Inhibition of LTßR signalling activates WNT-induced regeneration in lung.

Lymphotoxin ß-receptor (LTßR) signalling promotes lymphoid neogenesis and the development of tertiary lymphoid structures1,2, which are associated with severe chronic inflammatory diseases that span several organ systems3-6. How LTßR signalling drives chronic tissue damage particularly in the lung, the mechanism(s) that regulate this process, and whether LTßR blockade might be of therapeutic value have remained unclear. Here we demonstrate increased expression of LTßR ligands in adaptive and innate immune cells, enhanced non-canonical NF-κB signalling, and enriched LTßR target gene expression in lung epithelial cells from patients with smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke. Therapeutic inhibition of LTßR signalling in young and aged mice disrupted smoking-related inducible bronchus-associated lymphoid tissue, induced regeneration of lung tissue, and reverted airway fibrosis and systemic muscle wasting. Mechanistically, blockade of LTßR signalling dampened epithelial non-canonical activation of NF-κB, reduced TGFß signalling in airways, and induced regeneration by preventing epithelial cell death and activating WNT/ß-catenin signalling in alveolar epithelial progenitor cells. These findings suggest that inhibition of LTßR signalling represents a viable therapeutic option that combines prevention of tertiary lymphoid structures1 and inhibition of apoptosis with tissue-regenerative strategies.

Small Airway Disease in Pre-Chronic Obstructive Pulmonary Disease with Emphysema: A Cross-Sectional Study.

Rationale: Small airway disease is an important pathophysiological feature of chronic obstructive pulmonary disease (COPD). Recently, "pre-COPD" has been put forward as a potential precursor stage of COPD that is defined by abnormal spirometry findings or significant emphysema on computed tomography (CT) in the absence of airflow obstruction. Objective: To determine the degree and nature of (small) airway disease in pre-COPD using microCT in a cohort of explant lobes/lungs. Methods: We collected whole lungs/lung lobes from patients with emphysematous pre-COPD (n = 10); Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I (n = 6), II (n = 6), and III/IV (n = 7) COPD; and controls (n = 10), which were analyzed using CT and microCT. The degree of emphysema and the number and morphology of small airways were compared between groups, and further correlations were investigated with physiologic measures. Airway and parenchymal pathology was also validated with histopathology. Measurements and Main Results: The numbers of transitional bronchioles and terminal bronchioles per milliliter of lung were significantly lower in pre-COPD and GOLD stages I, II, and III/IV COPD compared with controls. In addition, the number of alveolar attachments of the transitional bronchioles and terminal bronchioles was also lower in pre-COPD and all COPD groups compared with controls. We did not find any differences between the pre-COPD and COPD groups in CT or microCT measures. The percentage of emphysema on CT showed the strongest correlation with the number of small airways in the COPD groups. Histopathology showed an increase in the mean chord length and a decrease in alveolar surface density in pre-COPD and all GOLD COPD stages compared with controls. Conclusions: Lungs of patients with emphysematous pre-COPD already show fewer small airways and airway remodeling even in the absence of physiologic airway obstruction.

Cardiac point-of-care ultrasound: Practical integration in the pediatric and neonatal intensive care settings.

Cardiac point-of-care ultrasound (POCUS) is a technology increasingly leveraged at the bedside by pediatric critical care and neonatology providers to identify real-time hemodynamic pathophysiology. We present a framework for (1) identifying the scope of cardiac POCUS within the clinical practice setting, (2) standardizing views for protocolized hemodynamic assessment relevant to pediatric critical illness and (3) integrating POCUS findings for therapeutic guidance. Within the review, we also discuss practical strengths and limitations to image acquisition and interpretation within the varied cardiac POCUS views. Finally, we explore unique considerations within the neonatal population.    Conclusion: Cardiac POCUS is a technology and tool that reveals important real-time information at the bedside of the critically ill child and infant. Understanding strengths and limitations of cardiac POCUS views and protocolizing an approach to answer focused clinical questions provides a framework for training and translation to clinical care. What is Known: • Ultrasound technology is now ubiquitous among pediatric critical care and neonatology settings, and growing literature supports an expanded role in not only procedural but also diagnostic applications. • Cardiac POCUS influences provider perception of pathophysiology and changes clinical management. What is New: • Effective cardiac POCUS training and subsequent translation to clinical practice should improve when clinical questions and protocolized approaches to image acquisition are standardized within a specialty. • Cardiac POCUS views have strengths and limitations which must be recognized when assessing the hemodynamic profile of a child or neonate.

Safety and Efficacy of Ethanol for Catheter Salvage and Central Line-Associated Bloodstream Infection Prophylaxis in Polyurethane Catheters in the PICU.

OBJECTIVES: Ethanol lock therapy (ELT) is a potential method of central catheter salvage following central line-associated bloodstream infection (CLABSI) although there is potential risk of catheter damage in polyurethane catheters. Further, there is limited efficacy data across the spectrum of common pediatric catheters, and published ELT protocols describe dwell times that are not feasible for critically ill children. We sought to evaluate the safety and efficacy of ELT in polyurethane catheters using brief (30 min to 2 hr) dwell times in our PICU. DESIGN: Investigational pilot study using historical control data. SETTING: PICU in quaternary care, free-standing children's hospital. INTERVENTIONS: ELT in polyurethane central venous catheters for catheter salvage. RESULTS: ELT with brief dwell times was used in 25 patients, 22 of whom were bacteremic. Ultimately 11 patients, comprising 14 catheters, were diagnosed with a primary CLABSI. The catheter salvage rate in primary CLABSI patients receiving ELT was 92% (13/14) and significantly higher than the salvage rate in patients receiving antibiotics alone (non-ELT) (62%, 39/64; mean difference 0.32, 95% CI [0.14-0.50], p = 0.03). The rate of catheter fracture in all patients receiving ELT was 8% (2/25) while the rate of fracture in the non-ELT group was 13% (8/64; mean difference -0.05, 95% CI [-0.18 to 0.09], p = 0.72). The rate of tissue plasminogen activator (tPA) use in the ELT group was 8% (2/25), whereas the rate of tPA use in the non-ELT group was significantly higher at 42% (26/64; mean difference -0.34, 95% CI [-0.49 to -0.17], p = 0.002). CONCLUSIONS: The use of ELT for catheter salvage and prophylaxis in the PICU is safe in a variety of polyurethane catheters. Dwell times ranging from 30 minutes to 2 hours were effective in sterilizing the catheters while allowing other therapies to continue. This approach may decrease the need for frequent line changes in a medically fragile pediatric population.

Evolution and Impact of a Diagnostic Point-of-Care Ultrasound Program in a PICU.

OBJECTIVES: To evaluate the impact of point-of-care ultrasound (POCUS) use on clinicians within a PICU and to assess infrastructural elements of our POCUS program development. DESIGN: Retrospective observational study. SETTING: Large academic, noncardiac PICU in the United States. SUBJECTS: Patients in a PICU who had diagnostic POCUS performed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between January 1, 2017, and December 31, 2022, 7201 diagnostic POCUS studies were ordered; 1930 (26.8%) had a quality assurance (QA) record generated in an independent POCUS QA database. The cardiac domain was most frequently imaged (81.0% of ordered studies, 81.2% of reviewed studies). POCUS images changed clinician understanding of pathophysiology in 563 of 1930 cases (29.2%); when this occurred, management was changed in 318 of 563 cases (56.5%). Cardiac POCUS studies altered clinician suspected pathophysiology in 30.1% of cases (472/1568), compared with 21.5% (91/362) in noncardiac studies (p = 0.06). Among cases where POCUS changed clinician understanding, management changed more often following cardiac than noncardiac POCUS (p = 0.02). Clinicians identified a need for cardiology consultation or complete echocardiograms in 294 of 1568 cardiac POCUS studies (18.8%). Orders for POCUS imaging increased by 94.9%, and revenue increased by 159.4%, from initial to final study year. QA database use by both clinicians and reviewers decreased annually as QA processes evolved in the setting of technologic growth and unit expansion. CONCLUSIONS: Diagnostic POCUS imaging in the PICU frequently yields information that alters diagnosis and changes management. As PICU POCUS use increased, QA processes evolved resulting in decreased use of our initial QA database. Modifications to QA processes are likely necessary as clinical contexts change over time.

Ultrasound in Cardiopulmonary Arrest and Resuscitation: Constructing Comprehensive Implementation Frameworks in High-Risk Settings.

OBJECTIVES: Information obtained from point-of-care ultrasound during cardiopulmonary arrest and resuscitation (POCUS-CA) can be used to identify underlying pathophysiology and provide life-sustaining interventions. However, integration of POCUS-CA into resuscitation care is inconsistent. We used expert consensus building methodology to help identify discrete barriers to clinical integration. We subsequently applied implementation science frameworks to generate generalizable strategies to overcome these barriers. MEASURES AND MAIN RESULTS: Two multidisciplinary expert working groups used KJ Reverse-Merlin consensus building method to identify and characterize barriers contributing to failed POCUS-CA utilization in a hypothetical future state. Identified barriers were organized into affinity groups. The Center for Implementation Research (CFIR) framework and Expert Recommendations for Implementing Change (CFIR-ERIC) tool were used to identify strategies to guide POCUS-US implementation. RESULTS: Sixteen multidisciplinary resuscitation content experts participated in the working groups and identified individual barriers, consolidated into 19 unique affinity groups that mapped 12 separate CFIR constructs, representing all 5 CFIR domains. The CFIR-ERIC tool identified the following strategies as most impactful to address barriers described in the affinity groups: identify and prepare champions, conduct local needs assessment, conduct local consensus discussions, and conduct educational meetings. CONCLUSIONS: KJ Reverse-Merlin consensus building identified multiple barriers to implementing POCUS-CA. Implementation science methodologies identified and prioritized strategies to overcome barriers and guide POCUS-CA implementation across diverse clinical settings.

The impact of the immune system on lung injury and regeneration in COPD.

COPD is a devastating respiratory condition that manifests via persistent inflammation, emphysema development and small airway remodelling. Lung regeneration is defined as the ability of the lung to repair itself after injury by the proliferation and differentiation of progenitor cell populations, and becomes impaired in the COPD lung as a consequence of cell intrinsic epithelial stem cell defects and signals from the micro-environment. Although the loss of structural integrity and lung regenerative capacity are critical for disease progression, our understanding of the cellular players and molecular pathways that hamper regeneration in COPD remains limited. Intriguingly, despite being a key driver of COPD pathogenesis, the role of the immune system in regulating lung regenerative mechanisms is understudied. In this review, we summarise recent evidence on the contribution of immune cells to lung injury and regeneration. We focus on four main axes: 1) the mechanisms via which myeloid cells cause alveolar degradation; 2) the formation of tertiary lymphoid structures and the production of autoreactive antibodies; 3) the consequences of inefficient apoptotic cell removal; and 4) the effects of innate and adaptive immune cell signalling on alveolar epithelial proliferation and differentiation. We finally provide insight on how recent technological advances in omics technologies and human ex vivo lung models can delineate immune cell-epithelium cross-talk and expedite precision pro-regenerative approaches toward reprogramming the alveolar immune niche to treat COPD.

RIPK1 kinase-dependent inflammation and cell death contribute to the pathogenesis of COPD.

BACKGROUND: Receptor-interacting protein kinase 1 (RIPK1) is a key mediator of regulated cell death (including apoptosis and necroptosis) and inflammation, both drivers of COPD pathogenesis. We aimed to define the contribution of RIPK1 kinase-dependent cell death and inflammation in the pathogenesis of COPD. METHODS: We assessed RIPK1 expression in single-cell RNA sequencing (RNA-seq) data from human and mouse lungs, and validated RIPK1 levels in lung tissue of COPD patients via immunohistochemistry. Next, we assessed the consequences of genetic and pharmacological inhibition of RIPK1 kinase activity in experimental COPD, using Ripk1 S25D/S25D kinase-deficient mice and the RIPK1 kinase inhibitor GSK'547. RESULTS: RIPK1 expression increased in alveolar type 1 (AT1), AT2, ciliated and neuroendocrine cells in human COPD. RIPK1 protein levels were significantly increased in airway epithelium of COPD patients compared with never-smokers and smokers without airflow limitation. In mice, exposure to cigarette smoke (CS) increased Ripk1 expression similarly in AT2 cells, and further in alveolar macrophages and T-cells. Genetic and/or pharmacological inhibition of RIPK1 kinase activity significantly attenuated airway inflammation upon acute and subacute CS exposure, as well as airway remodelling, emphysema, and apoptotic and necroptotic cell death upon chronic CS exposure. Similarly, pharmacological RIPK1 kinase inhibition significantly attenuated elastase-induced emphysema and lung function decline. Finally, RNA-seq on lung tissue of CS-exposed mice revealed downregulation of cell death and inflammatory pathways upon pharmacological RIPK1 kinase inhibition. CONCLUSIONS: RIPK1 kinase inhibition is protective in experimental models of COPD and may represent a novel promising therapeutic approach.

Aqp5-/- mice exhibit reduced maximal body O2 consumption under cold exposure, normal pulmonary gas exchange, and impaired formation of brown adipose tissue.

The fundamental body functions that determine maximal O2 uptake (V̇o2max) have not been studied in Aqp5-/- mice (aquaporin 5, AQP5). We measured V̇o2max to globally assess these functions and then investigated why it was found altered in Aqp5-/- mice. V̇o2max was measured by the Helox technique, which elicits maximal metabolic rate by intense cold exposure of the animals. We found V̇o2max reduced in Aqp5-/- mice by 20%-30% compared with wild-type (WT) mice. As AQP5 has been implicated to act as a membrane channel for respiratory gases, we studied whether this is caused by the known lack of AQP5 in the alveolar epithelial membranes of Aqp5-/- mice. Lung function parameters as well as arterial O2 saturation were normal and identical between Aqp5-/- and WT mice, indicating that AQP5 does not contribute to pulmonary O2 exchange. The cause for the decreased V̇o2max thus might be found in decreased O2 consumption of an intensely O2-consuming peripheral organ such as activated brown adipose tissue (BAT). We found indeed that absence of AQP5 greatly reduces the amount of interscapular BAT formed in response to 4 wk of cold exposure, from 63% in WT to 25% in Aqp5-/- animals. We conclude that lack of AQP5 does not affect pulmonary O2 exchange, but greatly inhibits transformation of white to brown adipose tissue. As under cold exposure, BAT is a major source of the animals' heat production, reduction of BAT likely causes the decrease in V̇o2max under this condition.

Identifying commonalities in definition and governance of point-of-care ultrasound within statements from medical organizations in the United States: A scoping review for a shared understanding.

This scoping review analyzed statements from 22 medical organizations in the United States to identify commonalities in the definition and governance of point-of-care ultrasound (POCUS). A total of 41 statements were included. The review found that the most commonly used elements in defining POCUS were "focused," "bedside," and "patient care." In terms of governance, consistent requirements included specific training programs, documentation in medical records, continuous quality assurance, and standards for credentialing and privileging. These findings suggest the existence of essential commonalities that could facilitate communication and the development of standardized POCUS programs in the future.

Establishing a risk assessment framework for point-of-care ultrasound.

Point-of-care ultrasound (POCUS) refers to the use of portable ultrasound (US) applications at the bedside, performed directly by the treating physician, for either diagnostic or procedure guidance purposes. It is being rapidly adopted by traditionally non-imaging medical specialties across the globe. Recent international evidence-based guidelines on POCUS for critically ill neonates and children were issued by the POCUS Working Group of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC). Currently there are no standardized national or international guidelines for its implementation into clinical practice or even the training curriculum to monitor quality assurance. Further, there are no definitions or methods of POCUS competency measurement across its varied clinical applications. CONCLUSION: The Hippocratic Oath suggests medical providers do no harm to their patients. In our continued quest to uphold this value, providers seeking solutions to clinical problems must often weigh the benefit of an intervention with the risk of harm to the patient. Technologies to guide diagnosis and medical management present unique considerations when assessing possible risk to the patient. Frequently risk extends beyond the patient and impacts providers and the institutions in which they practice. POCUS is an emerging technology increasingly incorporated in the care of children across varied clinical specialties. Concerns have been raised by clinical colleagues and regulatory agencies regarding appropriate POCUS use and oversight. We present a framework for assessing the risk of POCUS use in pediatrics and suggest methods of mitigating risk to optimize safety and outcomes for patients, providers, and institutions. WHAT IS KNOWN: • The use POCUS by traditionally non-imaging pediatric specialty physicians for both diagnostic and procedural guidance is rapidly increasing. • Although there are international guidelines for its indications, currently there is no standardized guidance on its implementation in clinical practice. WHAT IS NEW: • Although standards for pediatric specialty-specific POCUS curriculum and training to competency have not been defined, POCUS is likely to be most successfully incorporated in clinical care when programmatic infrastructural elements are present. • Risk assessment is a forward-thinking process and requires an imprecise calculus that integrates considerations of the technology, the provider, and the context in which medical care is delivered. Medicolegal considerations vary across countries and frequently change, requiring providers and institutions to understand local regulatory requirements and legal frameworks to mitigate the potential risks of POCUS.

Retrospective Assessment of Patient and Catheter Characteristics Associated With Malpositioned Central Venous Catheters in Pediatric Patients.

OBJECTIVES: The primary objective was to determine the prevalence and characteristics associated with malpositioned temporary, nontunneled central venous catheters (CVCs) placed via the internal jugular (IJ) and subclavian (SC) veins in pediatric patients. DESIGN: Single-center retrospective cohort study. SETTING: Quaternary academic PICU. PATIENTS: Children greater than 1 month to less than 18 years who had a CVC placed between January 2014 and December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the CVC tip position located on the first postprocedural radiograph. CVC tip was defined as follows: "recommended" (tip location between the carina and two vertebral bodies inferior to the carina), "high" (tip location between one and four vertebral bodies superior to the carina), "low" (tip position three or more vertebral bodies inferior to the carina), and "other" (tip grossly malpositioned). Seven hundred eighty-one CVCs were included: 481 (61.6%) were in "recommended" position, 157 (20.1%) were "high," 131 (16.8%) were "low," and 12 (1.5%) were "other." Multiple multinomial regression (referenced to "recommended" position) showed that left-sided catheters (adjusted odds ratio [aOR], 2.00, 95% CI 1.17-3.40) were associated with "high" CVC tip positions, whereas weight greater than or equal to 40 kg had decreased odds of having a "high" CVC tip compared with the reference (aOR, 0.45; 95% CI, 0.24-0.83). Further, weight category 20-40 kg (aOR, 2.42; 95% CI, 1.38-4.23) and females (aOR, 1.51; 95% CI, 1.01-2.26) were associated with "low" CVC tip positions. There was no difference in rates of central line-associated blood stream infection, venous thromboembolism, or tissue plasminogen activator usage or dose between the CVCs with tips outside and those within the recommended location. CONCLUSIONS: The prevalence of IJ and SC CVC tips outside of the recommended location was high. Left-sided catheters, patient weight, and sex were associated with malposition. Malpositioned catheters were not associated with increased harm.

Laryngeal Ultrasound Detects Vocal Fold Immobility in Adults: A Systematic Review.

Laryngeal ultrasound (US) is becoming widely accepted for assessing true vocal fold immobility (TVFI), a potential complication of laryngeal and thyroid surgery. The objective of this project is to perform a systematic review and meta-analysis of pooled evidence surrounding laryngeal US as a modality for diagnosing TVFI in adults at risk for the condition in comparison to laryngoscopy as a gold standard. Medical subject heading terms were used to search MEDLINE, Embase, Google Scholar, Web of Science, and the Cochrane Library for relevant citations from January 1, 2000, to June 30, 2020. Studies were included if they involved patients 16 years and older, where laryngeal US was compared to laryngoscopy for TVFI. Studies were excluded if there were insufficient data to compute a sensitivity/specificity table after attempting to contact the authors. Case reports, and case series were also excluded. The initial search returned 1357 citations. Of these, 109 were selected for review utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirty citations describing 6033 patients were included in the final meta-analysis. A bivariate random effects meta-analysis was performed, revealing a pooled sensitivity for laryngeal US of 0.95 (95% confidence interval [CI] 0.88-0.98), a specificity of 0.99 (95% CI 0.97-0.99), and a diagnostic odds ratio of 1328.2 (95% CI 294.0-5996.5). The area under the curve of the hierarchical summary receiver operating characteristic curve was 0.99 (95% CI 0.98-1.00). Laryngeal US demonstrates high sensitivity and specificity for detecting VFI in the hands of clinicians directly providing care to patients.

The association between carotid flow time and fluid responsiveness in children under general anesthesia.

BACKGROUND: Fluid administration in children undergoing surgery requires precision, however, determining fluid responsiveness can be challenging. Ultrasound has been used widely in the emergency department and intensive care units as a noninvasive, bedside manner of determining volume status, but the intraoperative period presents unique challenges as often the chest and abdomen are inaccessible for ultrasound. We investigate whether carotid artery ultrasound, specifically carotid flow time, can be used to determine fluid responsiveness in children under general anesthesia. METHODS: Prospective observational study of 87 children ages 1-12 years who were scheduled for elective noncardiac surgery. Ultrasound of the carotid artery and heart was performed at three time points: (1) after inhalational induction of anesthesia with the subject spontaneously breathing, (2) during positive pressure ventilation through endotracheal tube or supraglottic airway with tidal volume set at 8 ml/kg with PEEP of 10 cmH2 O, and (3) after a 10 ml/kg fluid bolus. Carotid flow time and cardiac output were measured from saved images. RESULTS: Corrected carotid flow time (FTc) increased with initiation of positive pressure ventilation in both fluid responders and nonresponders (352.7 vs. 365.3 msec, p = .005 in fluid responders; 348.3 vs. 365.2 msec, p = .001 in nonresponders). FTc increased after fluid bolus in both responders and nonresponders (365.3 vs. 397.6 msec, p < .001 in fluid responders; 365.2 vs. 397.2 msec, p < .001 in nonresponders). However, baseline FTc during spontaneous ventilation or positive pressure ventilation prior to fluid bolus was not associated with fluid responsiveness. DISCUSSION: Flow time increases with initiation of positive pressure ventilation and after administration of a fluid bolus. FTc may serve as an indicator of fluid status but does not predict fluid responsiveness in children under general anesthesia.

Green bonds and other assets: Evidence from extreme risk transmission.

Green bonds (GB) are gaining a prominent role in sustainable development because of their ability to fund environment-friendly projects. This study aims to investigate if investors can benefit from the risk diversification properties of including GB with other assets, particularly within the context of the ongoing COVID-19 pandemic. To do so, we utilize a quantile-connectedness approach to examine a set of GB and traditional assets, i.e., commodities, stocks, and bonds, from 2008 to 2020. We find higher total time-varying risk spillovers during extreme high volatility periods than those with average and low volatility. For pairwise risk spillovers, GB offers more diversification opportunities when volatility is very low. Nevertheless, the diversification benefits increase during the COVID period. The strong bidirectional risk spillovers between GB and conventional bonds imply that GB can be considered a good alternative to traditional bonds while benefiting from their diversification potential, particularly with energy and agriculture. Our findings are useful for investors wishing to implement green diversification portfolio strategies in extreme volatility periods and act as an encouragement to policymakers to establish efficient policies to promote green finance.

Left Ventricular Diastolic Dysfunction in Pediatric Sepsis: Outcomes in a Single-Center Retrospective Cohort Study.

OBJECTIVES: Left ventricular diastolic dysfunction is associated with difficulty in ventilator weaning and increased mortality in septic adults. We evaluated the association of left ventricular diastolic dysfunction with outcomes in a cohort of children with severe sepsis and septic shock. DESIGN: Retrospective cohort study. SETTING: Single-center noncardiac PICU. PATIENTS: Age greater than 1 month to less than 18 years old with severe sepsis or septic shock from January 2011 to June 2017 with echocardiogram within 48 hours of sepsis onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Echocardiograms were retrospectively assessed for mitral inflow E (early) and A (atrial) velocity and e' (early mitral annular motion) septal and lateral velocity. Left ventricular diastolic dysfunction was defined as E/e' greater than 10, E/A less than 0.8, or E/A greater than 1.5. Left ventricular diastolic dysfunction was present in 109 of 204 patients (53%). The data did not demonstrate an association between the presence of left ventricular diastolic dysfunction and the proportion of children requiring invasive mechanical ventilation at the time of echocardiogram (difference in proportion, +5% [72% vs 67%; 95% CI, -8% to 17%]; p = 0.52). The duration of mechanical ventilation was median 192.9 hours (interquartile range, 65.0-378.4 hr) in the left ventricular diastolic dysfunction group versus 151.0 hours (interquartile range, 45.7-244.3 hr) in the group without left ventricular diastolic dysfunction. The presence of left ventricular diastolic dysfunction was not significantly associated with ICU length of stay or mortality. Exploratory analyses revealed that an alternative definition of left ventricular diastolic dysfunction, solely defined by E/e' greater than 10, was found to have an association with mechanical ventilation requirement at the time of echocardiogram (difference in proportion, +15%; 95% CI, 3-28%; p = 0.02) and duration of mechanical ventilation (median, 207.3 vs 146.9 hr). CONCLUSIONS: The data failed to show an association between the presence of left ventricular diastolic dysfunction defined by both E/e' and E/A and the primary and secondary outcomes. When an alternative definition of left ventricular diastolic dysfunction with E/e' alone was used, there was a significant association with respiratory outcomes.

Assessment of Vocal Cord Motion Using Laryngeal Ultrasound in Children: A Systematic Review and Meta-Analysis.

OBJECTIVES: Laryngeal ultrasound is a nonirradiating, noninvasive method for assessing the upper airway in children. This systematic review and meta-analysis examine available evidence for accuracy of laryngeal ultrasound in diagnosing vocal cord immobility in infants and children after surgery and trauma affecting the vocal cords. DESIGN: Medical subject heading terms were used to search MEDLINE, Embase, Google Scholar, Web of Science, and the Cochrane Library for relevant citations. Publications from January 1, 2000, to June 30, 2020 were included in the search strategy. Study inclusion criteria consisted of randomized control trials and nonrandomized retrospective or prospective observational studies where vocal cord motion was evaluated by laryngeal ultrasound and compared with a reference test. Studies were excluded if there was insufficient data to compute a sensitivity/specificity table. Case reports, case series less than 10, and manuscripts not published in English were also excluded. PATIENTS: Studies which included subjects younger than or equal to 18 years were considered for full article review. SETTINGS: No restrictions on study settings were imposed in this systematic review. MEASUREMENTS AND MAIN RESULTS: The initial search returned 1,357 citations. After de-duplication, abstract, and full review, eight citations were included in the final meta-analysis. A bivariate random-effects meta-analysis was performed, which revealed a pooled sensitivity for laryngeal ultrasound in detecting vocal cord immobility of 91% (95% CI, 83-95%), specificity of 97% (95% CI, 82-100%), diagnostic odds ratio 333.56 (95% CI, 34.00-3,248.71), positive likelihood ratio 31.58 (95% CI, 4.50-222.05), and negative likelihood ratio 0.09 (95% CI, 0.05-0.19). CONCLUSIONS: Laryngeal ultrasound demonstrates high sensitivity and specificity for detecting vocal cord motion in children in a wide range of clinical settings. Laryngeal ultrasound offers a low-risk imaging option for assessing vocal cord function in children compared with the current gold standard of laryngoscopy.

A Call to Action for the Pediatric Critical Care Community.

Healthcare regulatory bodies have escalated concerns regarding the use of point-of-care ultrasound by nonradiology and noncardiology physicians. A recently published PCCMPerspective identified that data do not support many of these concerns and addressed common misconceptions associated with point-of-care ultrasound use in the critical care setting. Indeed, the global point-of-care ultrasound community and specifically the pediatric critical care community have the opportunity to be leaders in demonstrating how to translate new skills and technologies to the bedside in a safe and effective manner. We seek to extend the conversation and propose next steps in supporting integration of point-of-care ultrasound in pediatric critical care practice.

Integrating Focused Cardiac Ultrasound Into Pediatric Septic Shock Assessment.

OBJECTIVES: To assess focused cardiac ultrasound impact on clinician hemodynamic characterization of patients with suspected septic shock as well as expert-generated focused cardiac ultrasound algorithm performance. DESIGN: Retrospective, observational study. SETTING: Single-center, noncardiac PICU. PATIENTS: Less than 18 years old receiving focused cardiac ultrasound study within 72 hours of sepsis pathway initiation from January 2014 to December 2016. INTERVENTIONS: Hemodynamics of patients with suspected septic shock were characterized as fluid responsive, myocardial dysfunction, obstructive physiology, and/or reduced systemic vascular resistance by a bedside clinician before and immediately following focused cardiac ultrasound performance. The clinician's post-focused cardiac ultrasound hemodynamic assessments were compared with an expert-derived focused cardiac ultrasound algorithmic hemodynamic interpretation. Subsequent clinical management was assessed for alignment with focused cardiac ultrasound characterization and association with patient outcomes. MEASUREMENTS AND MAIN RESULTS: Seventy-one patients with suspected septic shock (median, 4.7 yr; interquartile range, 1.6-8.1) received clinician performed focused cardiac ultrasound study within 72 hours of sepsis pathway initiation (median, 2.1 hr; interquartile range, -1.5 to 11.8 hr). Two patients did not have pre-focused cardiac ultrasound and 23 patients did not have post-focused cardiac ultrasound hemodynamic characterization by clinicians resulting in exclusion from related analyses. Post-focused cardiac ultrasound clinician hemodynamic characterization differed from pre-focused cardiac ultrasound characterization in 67% of patients (31/46). There was substantial concordance between clinician's post-focused cardiac ultrasound and algorithm hemodynamic characterization (33/48; κ = 0.66; CI, 0.51-0.80). Fluid responsive (κ = 0.62; CI, 0.40-0.84), obstructive physiology (к = 0.87; CI, 0.64-1.00), and myocardial dysfunction (1.00; CI, 1.00-1.00) demonstrated substantial to perfect concordance. Management within 4 hours of focused cardiac ultrasound aligned with algorithm characterization in 53 of 71 patients (75%). Patients with aligned management were less likely to have a complicated course (14/52, 27%) compared with misaligned management (8/19, 42%; p = 0.25). CONCLUSIONS: Incorporation of focused cardiac ultrasound in the evaluation of patients with suspected septic shock frequently changed a clinician's characterization of hemodynamics. An expert-developed algorithm had substantial concordance with a clinician's post-focused cardiac ultrasound hemodynamic characterization. Management aligned with algorithm characterization may improve outcomes in children with suspected septic shock.