Biomarkers for the Discrimination of Acute Kawasaki Disease From Infections in Childhood

Funding Information: We would like to thank all the patients and their relatives as well as the treatment teams for their participation in this study. We also thank Dr. Mischa Keizer for his help in developing the MRP8/14 ELISA. We would like to thank the EUCLIDS Consortium, PERFORM Consortium, and the Genetic Determinants of Kawasaki Disease Study group (UK). Funding. This work was partially supported by the European Seventh Framework Program for Research and Technological Development (FP7) under EUCLIDS grant agreement no. 279185; from the European Union's Horizon 2020 research and innovation program under grant agreement no. 668303; by STINAFO and anonymous donor; and by Sanquin Blood Supply Product and Process Development Cellular Products Fund (PPOC 1957). Publisher Copyright: © Copyright © 2020 Zandstra, van de Geer, Tanck, van Stijn-Bringas Dimitriades, Aarts, Dietz, van Bruggen, Schweintzger, Zenz, Emonts, Zavadska, Pokorn, Usuf, Moll, Schlapbach, Carrol, Paulus, Tsolia, Fink, Yeung, Shimizu, Tremoulet, Galassini, Wright, Martinón-Torres, Herberg, Burns, Levin, Kuijpers, EUCLIDS Consortium, PERFORM Consortium and UK Kawasaki Disease Genetics Study Network. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Kawasaki disease (KD) is a vasculitis of early childhood mimicking several infectious diseases. Differentiation between KD and infectious diseases is essential as KD's most important complication—the development of coronary artery aneurysms (CAA)—can be largely avoided by timely treatment with intravenous immunoglobulins (IVIG). Currently, KD diagnosis is only based on clinical criteria. The aim of this study was to evaluate whether routine C-reactive protein (CRP) and additional inflammatory parameters myeloid-related protein 8/14 (MRP8/14 or S100A8/9) and human neutrophil-derived elastase (HNE) could distinguish KD from infectious diseases. Methods and Results: The cross-sectional study included KD patients and children with proven infections as well as febrile controls. Patients were recruited between July 2006 and December 2018 in Europe and USA. MRP8/14, CRP, and HNE were assessed for their discriminatory ability by multiple logistic regression analysis with backward selection and receiver operator characteristic (ROC) curves. In the discovery cohort, the combination of MRP8/14+CRP discriminated KD patients (n = 48) from patients with infection (n = 105), with area under the ROC curve (AUC) of 0.88. The HNE values did not improve discrimination. The first validation cohort confirmed the predictive value of MRP8/14+CRP to discriminate acute KD patients (n = 26) from those with infections (n = 150), with an AUC of 0.78. The second validation cohort of acute KD patients (n = 25) and febrile controls (n = 50) showed an AUC of 0.72, which improved to 0.84 when HNE was included. Conclusion: When used in combination, the plasma markers MRP8/14, CRP, and HNE may assist in the discrimination of KD from both proven and suspected infection.publishersversionPeer reviewe

CT Angiography or Cardiac MRI for Detection of Coronary Artery Aneurysms in Kawasaki Disease

Background: Kawasaki disease (KD) is an acute vasculitis that mainly affects the coronary arteries. This inflammation can cause coronary artery aneurysms (CAAs). Patients with KD need cardiac assessment for risk stratification for the development of myocardial ischemia, based on Z-score (luminal diameter of the coronary artery corrected for body surface area). Echocardiography is the primary imaging modality in KD but has several important limitations. Coronary computed tomographic angiography (cCTA) and Cardiac MRI (CMR) are non-invasive imaging modalities and of additional value for assessment of CAAs with a high diagnostic yield. The objective of this single center, retrospective study is to explore the diagnostic potential of coronary artery assessment of cCTA vs. CMR in children with KD. Methods and Results: Out of 965 KD patients from our database, a total of 111 cCTAs (104 patients) and 311 CMR (225 patients) have been performed since 2010. For comparison, we identified 54 KD patients who had undergone both cCTA and CMR. CMR only identified eight patients with CAAs compared to 14 patients by cCTA. CMR missed 50% of the CAAs identified by cCTA. Conclusions: Our single center study demonstrates that cCTA may be a more sensitive diagnostic tool to detect CAAs in KD patients, compared to CMR

Six Hours of Manual Ventilation With a Bag-Valve-Mask Device Is Feasible and Clinically Consistent

OBJECTIVES: Manual ventilation of intubated patients is a common intervention. It requires skill as well as physical effort and is typically restricted to brief periods. Prolonged manual ventilation may be unavoidable in some scenarios, for example, extreme mass casualty incidents. The present study tested whether nurses are capable of appropriately manually ventilating patients for 6 hours. DESIGN: Volunteers performed ventilation on an electronic simulator for 6 hours while their own cardiorespiratory variables and the quality of the delivered ventilation were measured and recorded. The volunteers scored their perceived level of effort on a standard Borg Scale. SETTING: Research laboratory at the Emergency Department, Tel Aviv Medical Center. SUBJECTS: Ten nursing staff members of the Tel Aviv Sourasky Medical Center, 25-43 years old. INTERVENTIONS: Volunteers ventilated manually a lung simulator for 6 hours. MEASUREMENTS AND MAIN RESULTS: The subjects' physiologic states, including blood pressure, heart rate, respiratory rate, and oxygen saturation, showed no significant changes over time. The quality of delivered ventilation was somewhat variable, but it was stable on the average: average tidal volume ranged between 524.8 and 607.0 mL (p = 0.33). There was a slight but significant increase (7.3-10.9 L/min [p = 0.048]) in minute volume throughout the test period, reaching values consistent with mild hyperventilation. The subjects scored their perceived working effort as very light to fairly light, with a nonsignificant gradual increase in the Borg score as the study progressed. CONCLUSIONS: Manual ventilation of intubated patients can be performed continuously for 6 hours without excessive physical effort on the part of the operator. The quality of delivered ventilation was clinically adequate for all of them. There was a mild but significant trend toward hyperventilation, albeit within safe clinical levels, which was due to an increasing ventilatory rate rather than an increase in tidal volume

Biomarkers for the Discrimination of Acute Kawasaki Disease From Infections in Childhood.

Background: Kawasaki disease (KD) is a vasculitis of early childhood mimicking several infectious diseases. Differentiation between KD and infectious diseases is essential as KD's most important complication-the development of coronary artery aneurysms (CAA)-can be largely avoided by timely treatment with intravenous immunoglobulins (IVIG). Currently, KD diagnosis is only based on clinical criteria. The aim of this study was to evaluate whether routine C-reactive protein (CRP) and additional inflammatory parameters myeloid-related protein 8/14 (MRP8/14 or S100A8/9) and human neutrophil-derived elastase (HNE) could distinguish KD from infectious diseases. Methods and Results: The cross-sectional study included KD patients and children with proven infections as well as febrile controls. Patients were recruited between July 2006 and December 2018 in Europe and USA. MRP8/14, CRP, and HNE were assessed for their discriminatory ability by multiple logistic regression analysis with backward selection and receiver operator characteristic (ROC) curves. In the discovery cohort, the combination of MRP8/14+CRP discriminated KD patients (n = 48) from patients with infection (n = 105), with area under the ROC curve (AUC) of 0.88. The HNE values did not improve discrimination. The first validation cohort confirmed the predictive value of MRP8/14+CRP to discriminate acute KD patients (n = 26) from those with infections (n = 150), with an AUC of 0.78. The second validation cohort of acute KD patients (n = 25) and febrile controls (n = 50) showed an AUC of 0.72, which improved to 0.84 when HNE was included. Conclusion: When used in combination, the plasma markers MRP8/14, CRP, and HNE may assist in the discrimination of KD from both proven and suspected infection