BACKGROUND:Children undergoing high-risk cardiac surgery face significant postoperative morbidity and mortality risk, and early recognition of impaired systemic perfusion is critical. Current monitoring modalities, such as lactate, central venous oxygen saturation, and near-infrared spectroscopy, are indirect surrogates of cardiac output and are either invasive or have limited predictive value. Perfusion index (PI) is a continuous, noninvasive measure derived from pulse oximetry that has shown promise in adult critical care but remains underexplored in pediatric cardiac surgery. We sought to determine whether postoperative PI is associated with morbidity and mortality in this high-risk population. METHODS:We conducted a retrospective cohort study of children (age 0-18 years) who underwent STAT 4-5 surgery between 2021 and 2024. High-resolution PI data from the first 24 postoperative hours were analyzed. Multivariable logistic regression was used to determine associations with mortality and secondary outcomes. RESULTS:Of the 223 patients in our cohort, 33 (14.8%) died before discharge and demonstrated significantly lower PI values across all time points. Higher median PI during the first 6 postoperative hours was associated with reduced mortality (adjusted odds ratio [aOR], 0.49; P = .042). An abnormal PI (<0.7) in the first 6 postoperative hours was associated with a 3-fold increase in mortality risk (aOR, 3.7; P = .004). Higher median PI over the first 6 hours also was linked to lower odds of dialysis, extracorporeal membrane oxygenation, or low cardiac output syndrome, as well as shorter intensive care unit and hospital stays. CONCLUSIONS:PI may be a useful early biomarker of adverse outcomes after high-risk pediatric cardiac surgery. Its continuous, noninvasive nature offers practical advantages over traditional measures and is complementary to other indirect measures. Multicenter prospective studies are needed.

OBJECTIVE:Fluid overload (FO) after pediatric cardiac surgery with cardiopulmonary bypass (CPB) is common and has been associated with poor outcomes. We aimed to describe the relationship between plasma concentrations of syndecan-1 (SD1), a biomarker of endothelial glycocalyx injury, and FO in a cohort of children undergoing cardiac surgery. DESIGN:Single-center prospective observational pilot study, 2022-2023. SETTING:Twenty-six-bed pediatric cardiac ICU (CICU) at a quaternary pediatric referral center. PATIENTS:Children younger than 18 years old undergoing Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery congenital heart surgery mortality category 3, 4, and 5 cardiac surgeries with CPB. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We enrolled 15 patients. Blood samples were collected preoperatively and 4 hours postoperatively, then processed for plasma. SD1 concentrations were measured using enzyme-linked immunosorbent assays and compared with fluid balance on postoperative days (PODs) 1, 2, 3, and peak. SD1 discriminated fluid balance of greater than or equal to 10% on POD-1, POD-2, and POD-3 with an area under the receiver operating characteristic curve (AUROC) of 0.74, 0.84, and 0.88, respectively. SD1 also discriminated peak fluid balance of greater than or equal to 10% occurring on any day over the first seven PODs with an AUROC of 0.94. Patients with greater than or equal to 10% fluid balance on POD-2 ( p = 0.037), POD-3 ( p = 0.020), or peak ( p = 0.021) had significantly elevated delta SD1 when compared with those reaching less than 10%. Fluid balance of greater than or equal to 10% on POD-2 was associated with adverse events including longer duration of mechanical ventilation and CICU stay. CONCLUSIONS:Plasma SD1 was associated with FO in pediatric patients undergoing high-risk cardiac surgery with CPB. Further studies exploring the clinical utility of SD1 as a biomarker for FO in the postoperative management of children who undergo cardiac surgery with CPB should be pursued.

OBJECTIVE:Sepsis remains a major cause of morbidity and mortality in children, necessitating an early risk assessment to prevent delayed treatment and achieve optimal outcomes. This study investigated the association between systemic immune-inflammatory indices and clinical outcomes in children with sepsis. DESIGN:Single-center, retrospective cohort study. SETTING:Pediatric intensive care unit of a tertiary care children's hospital from 2015 to 2023. PATIENTS:Children aged 0-18 years admitted with sepsis. Patients were excluded if they lacked a complete blood count with differential on admission. RESULTS:In total, 420 patients were included. The platelet-to-lymphocyte ratio (PLR) was associated with higher mortality [hazard ratio 1.001 (1.000-1.002), P  = 0.032]. Incorporating PLR into the Pediatric Index of Mortality score improved the model discrimination for mortality (area under the receiver operator characteristic curves 0.705 vs. 0.774; area under the precision-recall curve 0.202 vs. 0.257). Similarly, adding PLR to the Pediatric Risk of Mortality-III improved the area under the receiver operator characteristic curves from 0.648 to 0.697. High PLR was also associated with higher odds of requiring intubation (OR 2.42, P  = 0.005) and extracorporeal membrane oxygenation (OR 4.74, P  = 0.002) and with decreased subdistribution hazard ratio of extubation, intensive care unit discharge, and hospital discharge alive at 28 days (subdistribution hazard ratio 0.89, 0.72, and 0.76, respectively; all P  < 0.005). CONCLUSIONS:High PLR at admission was independently associated with worse clinical outcomes in pediatric patients with sepsis. Adding PLR to the Pediatric Index of Mortality and Pediatric Risk of Mortality-III enhanced the predictive performance. PLR is a simple and readily available index that may improve early risk stratification in this high-risk population.

Dhami, Jatinder1; Friedman, Matthew1; Chandhoke, Swati2; Moynihan, Katie3; Alizadeh, Faraz4; Cater, Daniel5 Author Information

Surviving beta cells in type 1 diabetes respond to inflammation by upregulating programmed death-ligand 1 (PD-L1) to engage immune cell programmed death protein 1 (PD-1) and limit destruction by self-reactive immune cells. Extracellular vesicles (EVs) and their cargo can serve as biomarkers of beta cell health and contribute to islet intercellular communication. We hypothesised that the inflammatory milieu of type 1 diabetes increases PD-L1 in beta cell EV cargo and that EV PD-L1 may protect beta cells against immune-mediated cell death. Beta cell lines and human islets were treated with proinflammatory cytokines to model the proinflammatory type 1 diabetes microenvironment. EVs were isolated using ultracentrifugation or size exclusion chromatography and analysed via immunoblot, flow cytometry and ELISA. EV PD-L1 binding to PD-1 was assessed using a competitive binding assay and in vitro functional assays testing the ability of EV PD-L1 to inhibit NOD CD8+ T cells. Plasma EV and soluble PD-L1 were assayed in the plasma of islet autoantibody-positive (Ab+) individuals or individuals with recent-onset type 1 diabetes and compared with levels in non-diabetic control individuals. PD-L1 protein co-localised with tetraspanin-associated proteins intracellularly and was detected on the surface of beta cell EVs. Treatment with IFN-α or IFN-γ for 24 h induced a twofold increase in EV PD-L1 cargo without a corresponding increase in the number of EVs. IFN exposure predominantly increased PD-L1 expression on the surface of beta cell EVs and beta cell EV PD-L1 showed a dose-dependent capacity to bind PD-1. Functional experiments demonstrated specific effects of beta cell EV PD-L1 to suppress proliferation and cytotoxicity of murine CD8+ T cells. Plasma EV PD-L1 levels were increased in Ab+individuals, particularly in those positive for a single autoantibody. Additionally, in Ab+ individuals or those who had type 1 diabetes, but not in control individuals, plasma EV PD-L1 positively correlated with circulating C-peptide, suggesting that higher EV PD-L1 could be protective for residual beta cell function. IFN exposure increases PD-L1 on the beta cell EV surface. Beta cell EV PD-L1 binds PD1 and inhibits CD8+ T cell proliferation and cytotoxicity. Circulating EV PD-L1 is higher in Ab+ individuals than in control individuals. Circulating EV PD-L1 levels correlate with residual C-peptide at different stages in type 1 diabetes progression. These findings suggest that EV PD-L1 could contribute to heterogeneity in type 1 diabetes progression and residual beta cell function and raise the possibility that EV PD-L1 could be exploited as a means to inhibit immune-mediated beta cell death.

S-nitrosothiols are endogenous, bioactive molecules. S-nitrosothiols are implicated in many diseases, including sepsis. It is currently cumbersome to measure S-nitrosothiols clinically. We have previously developed an instrument to measure tissue S-nitrosothiols non-invasively using ultraviolet light. We have performed a prospective case control study of controls and children with sepsis admitted to the PICU. We hypothesized that tissue S-nitrosothiols would be higher in septic patients than controls. Controls were patients with no cardiopulmonary instability. Cases were patients with septic shock. We measured S-nitrosothiols, both at diagnosis and after resolution of shock. A total of 44 patients were enrolled: 21 controls and 23 with sepsis. At baseline, the controls were younger [median age 5 years (IQR 0, 9) versus 11 years (IQR: 6, 16), p-value = 0.012], had fewer comorbidities [7 (33.3%) vs. 20 (87.0%), p-value < 0.001], and had lower PELOD scores [0 (IQR: 0, 0) vs. 12 (IQR: 11, 21), p-value < 0.001]. S-nitrosothiol levels were higher in sepsis cohort (1.1 ppb vs. 0.8 ppb, p = 0.004). Five patients with sepsis had longitudinal measures and had a downtrend after resolution of shock (1.3 ppb vs. 0.9 ppb, p = 0.04). We dichotomized patients based on S-nitrosothiol levels and found an association with worse clinical outcomes, but further work will be needed to validate these findings.

Kidney echogenicity is typically determined subjectively but may have a quantifiable relationship to kidney function. Similarly, kidney length has been shown to correlate with kidney function. This study sought to quantify echogenicity using readily available software. Secondarily, we aimed to evaluate the correlation between quantified echogenicity and kidney length to the estimated glomerular filtration rate (eGFR) in children with acute kidney injury (AKI) and chronic kidney disease (CKD). In a single-center retrospective observational study, echogenicity index (EI) was determined using a ratio of right kidney to liver mean pixel density. The kidney length ratio (KLR) was determined by the actual to predicted lengths of both kidneys. Both variables were correlated to eGFR using correlation analyses and predictive capacity was determined with receiver operating characteristic curve (ROC) analysis. Of 94 subjects, 46

Objectives: The objective of our study was to semiautomatically generate echocardiogram indices in pediatric sepsis using novel algorithms and determine which indices were associated with mortality. We hypothesized that strain and diastolic indices would be most associated with mortality. Design: Retrospective cohort study of children with sepsis from 2017 to 2022. Survivors and nonsurvivors were compared for echocardiogram indices. Multivariate Cox proportional hazard models were constructed for our primary outcome of in-hospital mortality. Linear regression was performed for secondary outcomes, which included multiple composite 28-day outcomes. Results: Of the 54 patients in the study, 9 (17%) died. Multiple echocardiogram indices of both right (RV) and left ventricles (LV) were associated with in-hospital mortality [RV GLS adjusted hazard ratio (aHR): 1.16 (1.03-1.29), P = 0.011; RV global longitudinal early diastolic strain rate (GLSre) aHR: 0.24 (0.07 to 0.75), P = 0.014; LV GLSre aHR: 0.33 (0.11-0.97), P = 0.044]. Impairment in GLS was associated with fewer ventilator-free days [RV GLS beta-coefficient: -0.47 (-0.84 to -0.10), P = 0.013; LV GLS beta-coefficient -0.62 (-1.07 to -0.17), P = 0.008], organ-support free days [RV GLS beta-coefficient: -0.49 (-0.87 to -0.11), P = 0.013; LV GLS beta-coefficient: -0.64 (-1.10 to -0.17), P = 0.008], and days free from ICU [RV GLS beta-coefficient: -0.42 (-0.79 to -0.05), P = 0.026; LV GLS beta-coefficient: -0.58 (-1.03 to -0.13), P = 0.012]. Systolic indices were not associated with mortality in this cohort. Conclusion: Our study demonstrates the feasibility of obtaining echocardiogram indices in a semiautomatic method using our algorithms. We showed that abnormal strain is associated with worse outcomes in a cohort of children with sepsis.

Introduction: Sepsis induced myocardial dysfunction is common in pediatric sepsis. We sought to utilize novel, specialized algorithms of echocardiogram data that allow for automatic acquisition of echocardiographic indices from all four chambers without advanced interpretation by cardiologists. We hypothesized that these algorithms could predict mortality and morbidity in septic children. Methods: A retrospective cohort study of 59 children admitted to the ICU with sepsis and echocardiogram data. Three user inputted points outlining each heart chamber were applied to existing echocardiograms. Novel algorithms then computed the relevant echocardiographic indices. We examined right and left sided indices for systolic function [ejection fraction (EF), stroke volume (SV) systolic wave (S’)], diastolic function [early diastolic annular velocity (E’), late diastolic annular velocity (A’)], chamber sizes, and strain indices. Our primary outcome was mortality, secondary outcomes included ventilator free days (VFD) at 28 days, and length of stay (LOS). Linear regression models were constructed. Results: Six (10.2%) of 59 patients died. Baseline characteristics were similar between survivors and nonsurvivors. Survivors had higher right ventricular (RV) SV [11.2 mL (4.7, 52.3) versus 3.04 mL (2.1, 4.2), p=0.010], RV (S’) [6.2 cm/s (5.0, 7.6) versus 4.5 cm/s (2.9, 6.2), p=0.046] and RV end-diastolic volume (EDV) [29.6 mL (12.3, 70.9) versus 9.1 mL (5.8, 17.6), p=0.016]. Multiple right chamber indices were associated with more VFD at 28 days [RV S’: β 2.7 (1.3 to 4.1), p=< 0.000, RV E’: β 2.3 (0.9 to 3.6), p=0.002, right atrial (RA) SV: β 0.3 (0.1 to 0.5), p=0.010, RA EF: β 0.2 (0.0 to 0.4) p=0.047, and RA EDV: β 0.4 (0.1 to 0.8) p=0.017]. Multiple diastolic indices were associated with differences in both ICU LOS in hours [left ventricular (LV) A’: β -129.5 (-208.4 to -50.6), p=0.020; RV S’: β -96.1 (-168.7 to -23.4), p=0.01] and hospital LOS in hours [LV A’: β -144.9 (-266.6 to -23.4), p=0.02; RV S’: β -145.1 (-260.7 to -29.6), p=0.015]. Conclusions: In this cohort of children with sepsis, echocardiographic indices as measured by our point of care, novel algorithms can be utilized to risk stratify these high-risk patients. Right sided chambers appear to be more predictive of both mortality and morbidity.

Introduction: This study aimed to determine if a respiratory therapist (RT)-driven high flow nasal cannula (HFNC) protocol could decrease duration of HFNC use, pediatric intensive care unit (PICU) and hospital length of stay (LOS), and duration of continuous albuterol use in pediatric patients with critical asthma. Methods: This was a quality improvement project performed at a quaternary academic PICU. Patients admitted to the PICU between 2 and 18 years of age with a diagnosis of asthma requiring continuous albuterol and HFNC were included. Implementation of a RT-driven HFNC protocol [Plan-Do-Study-Act (PDSA) 1] occurred in October 2017. Additional interventions included weaning continuous albuterol and HFNC simultaneously (PDSA 2; March 2019), adjusting HFNC wean rate (PDSA 3; July 2020), and a HFNC holiday (PDSA 4; October 2021). HFNC duration was the primary outcome. Secondary outcomes included LOS data and continuous albuterol duration. Noninvasive ventilation (NIV), invasive mechanical ventilation (IMV), and 7-day PICU and hospital readmission rates were balancing measures. Results: 410 patients were included. Patient demographics and adjunct therapy use did not differ among the groups. HFNC duration decreased from 26.8 to 18.1 hours, both PICU and hospital LOS were decreased (41 to 31.8 hours, and 86.5 to 68 hours respectively) after PDSA 2. These outcomes remained stable during PDSA 3 and 4. Continuous albuterol duration and NIV use remained stable, while IMV use decreased throughout the study. Conclusions: An RT-driven HFNC protocol led to an improvement in clinical outcomes for pediatric patients with critical asthma without an increase in adverse events.