Gastrointestinal Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

CONTEXT Prior criteria to define pediatric multiple organ dysfunction syndrome (MODS) did not include gastrointestinal dysfunction. OBJECTIVES Our objective was to evaluate current evidence and to develop consensus criteria for gastrointestinal dysfunction in critically ill children. DATA SOURCES Electronic searches of PubMed and EMBASE were conducted from January 1992 to January 2020, using medical subject heading terms and text words to define gastrointestinal dysfunction, pediatric critical illness, and outcomes. STUDY SELECTION Studies were included if they evaluated critically ill children with gastrointestinal dysfunction, performance characteristics of assessment/scoring tools to screen for gastrointestinal dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies of adults or premature infants, animal studies, reviews/commentaries, case series with sample size ≤10, and non-English language studies with inability to determine eligibility criteria were excluded. DATA EXTRACTION Data were abstracted from each eligible study into a standard data extraction form along with risk of bias assessment by a task force member. RESULTS The systematic review supports the following criteria for severe gastrointestinal dysfunction: 1a) bowel perforation, 1b) pneumatosis intestinalis, or 1c) bowel ischemia, present on plain abdominal radiograph, computed tomography (CT) scan, magnetic resonance imaging (MRI), or gross surgical inspection, or 2) rectal sloughing of gut mucosa. LIMITATIONS The validity of the consensus criteria for gastrointestinal dysfunction are limited by the quantity and quality of current evidence. CONCLUSIONS Understanding the role of gastrointestinal dysfunction in the pathophysiology and outcomes of MODS is important in pediatric critical illness

Exuberant fibroblast activity compromises lung function via ADAMTS4

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Severe respiratory infections can result in acute respiratory distress syndrome (ARDS)1. There are no effective pharmacological therapies that have been shown to improve outcomes for patients with ARDS. Although the host inflammatory response limits spread of and eventually clears the pathogen, immunopathology is a major contributor to tissue damage and ARDS1,2. Here we demonstrate that respiratory viral infection induces distinct fibroblast activation states, which we term extracellular matrix (ECM)-synthesizing, damage-responsive and interferon-responsive states. We provide evidence that excess activity of damage-responsive lung fibroblasts drives lethal immunopathology during severe influenza virus infection. By producing ECM-remodelling enzymes—in particular the ECM protease ADAMTS4—and inflammatory cytokines, damage-responsive fibroblasts modify the lung microenvironment to promote robust immune cell infiltration at the expense of lung function. In three cohorts of human participants, the levels of ADAMTS4 in the lower respiratory tract were associated with the severity of infection with seasonal or avian influenza virus. A therapeutic agent that targets the ECM protease activity of damage-responsive lung fibroblasts could provide a promising approach to preserving lung function and improving clinical outcomes following severe respiratory infections

Publisher Correction: Exuberant fibroblast activity compromises lung function via ADAMTS4 (Nature, (2020), 587, 7834, (466-471), 10.1038/s41586-020-2877-5)

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. An amendment to this paper has been published and can be accessed via a link at the top of the paper

Improving benchmarking by using an explicit framework for the development of composite indicators: an example using pediatric quality of care

<p>Abstract</p> <p>Background</p> <p>The measurement of healthcare provider performance is becoming more widespread. Physicians have been guarded about performance measurement, in part because the methodology for comparative measurement of care quality is underdeveloped. Comprehensive quality improvement will require comprehensive measurement, implying the aggregation of multiple quality metrics into composite indicators.</p> <p>Objective</p> <p>To present a conceptual framework to develop comprehensive, robust, and transparent composite indicators of pediatric care quality, and to highlight aspects specific to quality measurement in children.</p> <p>Methods</p> <p>We reviewed the scientific literature on composite indicator development, health systems, and quality measurement in the pediatric healthcare setting. Frameworks were selected for explicitness and applicability to a hospital-based measurement system.</p> <p>Results</p> <p>We synthesized various frameworks into a comprehensive model for the development of composite indicators of quality of care. Among its key premises, the model proposes identifying structural, process, and outcome metrics for each of the Institute of Medicine's six domains of quality (safety, effectiveness, efficiency, patient-centeredness, timeliness, and equity) and presents a step-by-step framework for embedding the quality of care measurement model into composite indicator development.</p> <p>Conclusions</p> <p>The framework presented offers researchers an explicit path to composite indicator development. Without a scientifically robust and comprehensive approach to measurement of the quality of healthcare, performance measurement will ultimately fail to achieve its quality improvement goals.</p

Risk factors for health impairments in children after hospitalization for acute COVID-19 or MIS-C

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 <21-years-old hospitalized for acute COVID-19 or MIS-C (May 2020 to March 2022) surveyed 2- to 4-months post-admission. Multivariable regression was used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI).ResultsOf 232 children with acute COVID-19, 71 (30.6%) had persistent symptoms and 50 (21.6%) had activity impairments at follow-up; for MIS-C (n = 241), 56 (23.2%) had persistent symptoms and 58 (24.1%) had activity impairments. In adjusted analyses of patients with acute COVID-19, receipt of mechanical ventilation was associated with persistent symptoms [aRR 1.83 (95% CI: 1.07, 3.13)] whereas obesity [aRR 2.18 (95% CI: 1.05, 4.51)] and greater organ system involvement [aRR 1.35 (95% CI: 1.13, 1.61)] were associated with activity impairment. For patients with MIS-C, having a pre-existing respiratory condition was associated with persistent symptoms [aRR 3.04 (95% CI: 1.70, 5.41)] whereas obesity [aRR 1.86 (95% CI: 1.09, 3.15)] and greater organ system involvement [aRR 1.26 (1.00, 1.58)] were associated with activity impairments.DiscussionAmong patients hospitalized, nearly one in three hospitalized with acute COVID-19 and one in four hospitalized with MIS-C had persistent impairments for ≥2 months post-hospitalization. Persistent impairments were associated with more severe illness and underlying health conditions, identifying populations to target for follow-up

Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.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 <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19–related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown

Dynamics of Gut Microbiota Recovery after Antibiotic Exposure in Young and Old Mice (A Pilot Study)

Antibiotics have improved survival from previously deadly infectious diseases. Antibiotics alter the microbial composition of the gut microbiota, and these changes are associated with diminished innate immunity and decline in cognitive function in older adults. The composition of the human microbiota changes with age over the human lifespan. In this pilot study, we sought to identify if age is associated with differential recovery of the microbiota after antibiotic exposure. Using 16S rRNA gene sequencing, we compared recovery of the gut microbiota after the 10-day broad-spectrum antibiotic treatment in wild-type C57BL/six young and older mice. Immediately after antibiotic cessation, as expected, the number of ASVs, representing taxonomic richness, in both young and older mice significantly declined from the baseline. Mice were followed up to 6 months after cessation of the single 10-day antibiotic regimen. The Bray-Curtis index recovered within 20 days after antibiotic cessation in young mice, whereas in older mice the microbiota did not fully recover during the 6-months of follow-up. Bifidobacterium, Dubosiella, Lachnospiraceae_NK4A136_group became dominant in older mice, whereas in young mice, the bacteria were more evenly distributed, with only one dominant genus of Anaeroplasma. From 45 genera that became extinct after antibiotic treatment in young mice, 31 (68.9%) did not recover by the end of the study. In older mice, from 36 extinct genera, 27 (75%) did not recover. The majority of the genera that became extinct and never recovered belonged to Firmicutes phylum and Clostridiales family. In our study, age was a factor associated with the long-term recovery of the gut microbiota after the 10-day antibiotic treatment

Existing data analysis in pediatric critical care research

Our objectives were to review and categorize the existing data sources that are important to pediatric critical care medicine (PCCM) investigators and the types of questions that have been or could be studied with each data source. We conducted a narrative review of the medical literature, categorized the data sources available to PCCM investigators, and created an online data source registry. We found that many data sources are available for research in PCCM. To date, PCCM investigators have most often relied on pediatric critical care registries and treatment- or disease-specific registries. The available data sources vary widely in the level of clinical detail and the types of questions they can reliably answer. Linkage of data sources can expand the types of questions that a data source can be used to study. Careful matching of the scientific question to the best available data source or linked data sources is necessary. In addition, rigorous application of the best available analysis techniques and reporting consistent with observational research standards will maximize the quality of research using existing data in PCCM

The Association of Nutrition Status Expressed as Body Mass Index z Score With Outcomes in Children With Severe Sepsis: A Secondary Analysis From the Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study.

OBJECTIVES: The impact of nutrition status on outcomes in pediatric severe sepsis is unclear. We studied the association of nutrition status (expressed as body mass index z score) with outcomes in pediatric severe sepsis. DESIGN: Secondary analysis of the Sepsis Prevalence, Outcomes, and Therapies study. Patient characteristics, ICU interventions, and outcomes were compared across nutrition status categories (expressed as age- and sex-adjusted body mass index z scores using World Health Organization standards). Multivariable regression models were developed to determine adjusted differences in all-cause ICU mortality and ICU length of stay by nutrition status. SETTING: One-hundred twenty-eight PICUs across 26 countries. PATIENTS: Children less than 18 years with severe sepsis enrolled in the Sepsis Prevalence, Outcomes, and Therapies study (n = 567). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nutrition status data were available for 417 patients. Severe undernutrition was seen in Europe (25%), Asia (20%), South Africa (17%), and South America (10%), with severe overnutrition seen in Australia/New Zealand (17%) and North America (14%). Severe undernutrition was independently associated with all-cause ICU mortality (adjusted odds ratio, 3.0; 95% CI, 1.2-7.7; p = 0.02), whereas severe overnutrition in survivors was independently associated with longer ICU length of stay (1.6 d; p = 0.01). CONCLUSIONS: There is considerable variation in nutrition status for children with severe sepsis treated across this selected network of PICUs from different geographic regions. Severe undernutrition was independently associated with higher all-cause ICU mortality in children with severe sepsis. Severe overnutrition was independently associated with greater ICU length of stay in childhood survivors of severe sepsis