Search

Key Points: Question: How should children with suspected infection at higher risk of mortality, indicative of sepsis, be identified? Findings: Using an international survey, systematic review, and analysis of more than 3 million pediatric health care encounters, and consensus process, new criteria for sepsis and septic shock in children were developed. Pediatric sepsis in children (<18 years) with suspected infection was identified by at least 2 points in the novel Phoenix Sepsis Score, including dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems; and septic shock as sepsis with at least 1 cardiovascular point in the Phoenix Sepsis Score. Meaning: The new criteria for pediatric sepsis and septic shock are globally applicable. Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4—respiratory, cardiovascular, coagulation, and/or neurological—organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world. This article revises criteria to identify sepsis in children after an exhaustive process that involved surveying clinicians, reviewing health record databases, conducting a systematic review and meta-analysis, and undergoing a Delphi consensus process. [ABSTRACT FROM AUTHOR]

Key Points: Question: What are the best-performing organ dysfunction–based criteria to implement the definition of sepsis and septic shock in children with suspected infection? Findings: In this international, multicenter, retrospective cohort study including more than 3.6 million pediatric encounters, a novel score, the Phoenix Sepsis Score, was derived and validated to predict mortality in children with suspected or confirmed infection. The new criteria for pediatric sepsis and septic shock based on the score performed better than existing organ dysfunction scores and the International Pediatric Sepsis Consensus Conference criteria. Meaning: The new data-driven criteria for pediatric sepsis and septic shock based on measures of organ dysfunction had improved performance compared with prior pediatric sepsis criteria. Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria. This cohort study derives and validates novel criteria for diagnosis of pediatric sepsis and septic shock across high-resource and low-resource international settings. [ABSTRACT FROM AUTHOR]

Context Chronic stress is a risk factor for preterm birth; however, objective measures of stress in pregnancy are limited. Maternal stress biomarkers may fill this gap. Steroid hormones and neurosteroids such as allopregnanolone (ALLO) play important roles in stress physiology and pregnancy maintenance and therefore may be promising for preterm birth prediction. Objective We evaluated maternal serum ALLO, progesterone, cortisol, cortisone, pregnanolone, and epipregnanolone twice in gestation to evaluate associations with preterm birth. Methods We performed a nested case-control study using biobanked fasting serum samples from the Healthy Start prebirth cohort. We included healthy women with a singleton pregnancy and matched preterm cases with term controls (1:1; N = 27 per group). We used a new HPLC-tandem mass spectrometry assay to quantify ALLO and five related steroids. We used ANOVA, Fisher exact, χ2, t test, and linear and logistic regression as statistical tests. Results Maternal serum ALLO did not associate with preterm birth nor differ between groups. Mean cortisol levels were significantly higher in the preterm group early in pregnancy (13w0d-18w0d; P < 0.05) and higher early pregnancy cortisol associated with increased odds of preterm birth (at 13w0d; odds ratio, 1.007; 95% CI, 1.0002-1.014). Progesterone, cortisone, pregnanolone, and epipregnanolone did not associate with preterm birth. Conclusion The findings from our pilot study suggest potential utility of cortisol as a maternal serum biomarker for preterm birth risk assessment in early pregnancy. Further evaluation using larger cohorts and additional gestational timepoints for ALLO and the other analytes may be informative. [ABSTRACT FROM AUTHOR]

Background and Purpose: The gold standard for imaging of meningiomas is MRI with gadolinium‐based contrast agent. Due to increased costs, time, and uncertain chronic effects of gadolinium exposure, use of noncontrast T2‐weighted imaging (T2WI) in lieu of contrast‐enhanced MRI has been an increasing focus of research across various diagnostic scenarios. The purpose of this study was to evaluate the diagnostic accuracy of T2WI in detecting changes in meningioma tumor volume. Methods: Imaging and clinical data were reviewed for 82 consecutive patients undergoing MR‐surveillance of intracranial meningioma. Using volumetric‐T2WI, two neuroradiologists independently calculated tumor volumes. Measurements were compared to a baseline study contrast‐enhanced T1 tumor volume. Using contrast‐enhanced sequences as the reference standard, statistical analysis was performed to determine the accuracy of T2WI in detecting changes of meningioma volume. Results: Using only T2WI, readers detected meningioma volume change ≥ 20% in 19/82 patients and volume change <20% in 63/82 patients. Reader accuracy for detecting change in tumor volume on T2WI ≥ 20% was 0.85, sensitivity 0.65, specificity 0.93, positive predictive value (PPV) 0.79, and negative predictive value (NPV) 0.87. For meningiomas >1 ml, reader accuracy for detecting change in tumor volume on T2WI ≥20% was 0.90, sensitivity 0.78, specificity 0.95, PPV 0.88, and NPV 0.91. Change in tumor volume on T2WI ≥20% was detected with 100% accuracy for posterior fossa meningiomas. Inter‐reader agreement for all meningiomas was moderate (κ = 0.45) improving to substantial agreement (κ = 0.77) with tumor volumes >1 ml. Conclusion: Volumetric‐T2WI detects changes in meningioma volume with comparable accuracy to gold standard T1 postcontrast imaging, particularly with higher tumor volumes and posterior fossa locations. [ABSTRACT FROM AUTHOR]