A novel risk classification system for 30-day mortality in children undergoing surgery

<div><p>A simple, objective and accurate way of grouping children undergoing surgery into clinically relevant risk groups is needed. The purpose of this study, is to develop and validate a preoperative risk classification system for postsurgical 30-day mortality for children undergoing a wide variety of operations. The National Surgical Quality Improvement Project-Pediatric participant use file data for calendar years 2012–2014 was analyzed to determine preoperative variables most associated with death within 30 days of operation (D30). Risk groups were created using classification tree analysis based on these preoperative variables. The resulting risk groups were validated using 2015 data, and applied to neonates and higher risk CPT codes to determine validity in high-risk subpopulations. A five-level risk classification was found to be most accurate. The preoperative need for ventilation, oxygen support, inotropic support, sepsis, the need for emergent surgery and a do not resuscitate order defined non-overlapping groups with observed rates of D30 that vary from 0.075% (Very Low Risk) to 38.6% (Very High Risk). When CPT codes where death was never observed are eliminated or when the system is applied to neonates, the groupings remained predictive of death in an ordinal manner.</p></div

Observed mortality by risk group for sub groups.

<p>The observed mortality is plotted logarithmically by group. A = Very Low, B = Moderately Low, C = Moderately High, D = High, E = Very High. Each bar represents the estimate of the risk and confidence interval. The arrow is the observed rate for all patients from 2012–2015.</p

Preoperative therapy and risk for death after surgery.

<p>Preoperative therapy and risk for death after surgery.</p

Surgical mortality risk groups for children.

<p>Surgical mortality risk groups for children.</p

Patient characteristics and risk for death after surgery.

<p>Patient characteristics and risk for death after surgery.</p

Parsimonious LR model built on variables selected by classification tree analysis.

<p>Parsimonious LR model built on variables selected by classification tree analysis.</p

Comorbidities and risk for death after surgery.

<p>Comorbidities and risk for death after surgery.</p

Modulation of IL-33 levels during primary RSV infection alters ILC2 numbers and IL-13 production at 1 dpi.

<p>(<b>a</b>) Number of ILC2s (lineage^- CD45⁺ ICOS⁺ ST2⁺) expressed as percentage of total lung cells and MFI of surface ST2 on ILC2s at 1 dpi in neonatal mice pretreated with IL-33 neutralizing antibody (α-IL-33 + NR) or control IgG antibody (Isotype + NR) and adult mice pretreated with recombinant IL-33 (rIL-33 + AR) or vehicle control (Control + AR). (<i>n</i> = 5–7 per group). (<b>b</b>) IL-13 protein levels in whole lung homogenates. (<b>c</b>) Pulmonary viral loads measured at 4 dpi (peak) using the TCID₅₀ method. *<i>P</i> < 0.05 vs. indicated group, (Student’s <i>t</i>-test). Data are representative of two independent experiments (means ± s.e.m).</p

IL-33 and IL-13 concentrations are elevated in nasal aspirates from infants hospitalized with RSV infection.

<p>(<b>a</b>) Concentrations of IL-33 and IL-13 in nasal aspirates taken from RSV-infected infants (<i>n</i> = 19) on the first day (d1) of clinical presentation to Le Bonheur Children’s Hospital and again four weeks later (d28). (<b>b</b>) Correlation of IL-33 and IL-13 concentrations for all patients with d1 samples (<i>n</i> = 81). Samples with cytokine concentrations below the LOD of the assay are replaced by a value equal to the LOD divided by the square root of 2, and denoted with a filled circle. *<i>P</i> < 0.05 (Sign test (<b>a</b>) or Kendall’s tau correlation (<b>b</b>)).</p

RSV induces robust, rapid IL-33 and IL-13 production in the lungs of neonates.

<p>(<b>a</b>) Cytokine protein levels of IL-33 and IL-13 in whole lung homogenates of RSV-infected neonate (5-day-old; NR) and adult (6-8-week-old; AR) mice (<i>n</i> = 4–10 per group) at different days (0–10) post-infection (dpi). (<b>b</b>) Cytokine protein levels of IL-33 detected in BAL at 1 dpi from NR and AR mice (<i>n</i> = 8–10 per group) compared to controls. (<b>c</b>) Gating strategy for determination of IL-33 expression by median fluorescence intensity (MFI) in epithelial cells (CD45^- EpCam⁺) with representative IL-33 MFI histogram (quantified in inset vs. fluorescence-minus-one (FMO) control (dotted line)). (<b>d</b>) Representative micrographs of <i>in situ</i> hybridization for IL-33 mRNA with red arrows to indicate positive staining cells (top), magnified inset (bottom), and quantification of IL-33 mRNA positive cells per unit area of lung. Scale bar = 100 μm. (<b>e</b>) Cytokine protein levels of IL-33 in whole lung homogenates of neonates infected with RSV or UV-RSV compared to control at 1 dpi. *<i>P</i> < 0.05 (Student’s <i>t</i>-test; <b>a</b>, <b>c</b>, <b>d</b>) (Two-way ANOVA; <b>b</b>) (One-way ANOVA; <b>e</b>). Data are representative of two (<b>a</b>, <b>c</b>) or 2 pooled (<b>b</b>, <b>d</b>, <b>e</b>) independent experiments (means ± s.e.m).</p