Predictive Factors for Delayed Surgical Intervention in Children With Epidural Hematomas.

BACKGROUND: Optimal treatment of children with traumatic intracranial epidural hematomas (EDHs) is unknown. We sought to identify clinical and radiographic predictors of delayed surgical intervention among children with EDH admitted for observation. METHODS: We retrospectively identified patients younger than 15 years with acute traumatic EDHs evaluated at our level 1 pediatric trauma center. We excluded patients with penetrating head injuries, recent surgical evacuation of EDH, or depressed skull fracture requiring surgical repair and assigned the remaining subjects to the immediate surgery group if they underwent immediate surgical evacuation, to the supportive-therapy-only group if they underwent observation only, and to the delayed surgery group if they underwent surgery after observation. We abstracted clinical and laboratory findings, surgical interventions, and neurological outcome and measured EDH dimensions and volumes, adjusting for cranial size. We compared clinical and radiographic characteristics among groups and performed receiver-operator characteristic analyses of predictors of delayed surgery. RESULTS: Of 172 patients with EDH, 103 patients met the inclusion criteria, with 6 (6%) in the immediate surgery group, 87 (84%) in the supportive-therapy-only group, and 10 (10%) in the delayed surgery group. Headache, prothrombin time of >14 seconds, EDH maximal thickness of ≥1.1 cm, volume of ≥14 mL, EDH thickness/cranial width index of ≥0.08 and EDH volume/cranial volume index of ≥0.18, and mass effect were associated with delayed surgical intervention. There was no difference in length of stay or functional impairment between the immediate and delayed surgery groups. However, patients in delayed surgery group were more likely to have subjective symptoms at discharge than those in immediate surgery group. CONCLUSIONS: Among patients with EDH admitted for observation, larger EDH, mass effect, headaches, and prothrombin time of >14 seconds were associated with delayed surgical intervention. A larger-scale study is warranted to identify independent predictors of delayed surgery in children under observation for EDH.

Emergence of Extended-Spectrum ß-Lactamase-Producing Pathogens in Community-Acquired Urinary Tract Infections Among Infants at a Pediatric Emergency Department.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing pathogens are common among adults and are associated with extended and multiple hospitalizations. They cause urinary tract infections (UTIs) among children with known risk factors such as urinary tract abnormalities and antimicrobial prophylaxis. The emergence of UTIs caused by ESBL-producing organisms among infants has not been well characterized. OBJECTIVE: We sought to describe the incidence and current clinical management of infants who were diagnosed with UTIs caused by ESBL-producing organisms at a pediatric emergency department (ED). In addition, we sought to describe risk factors associated with inpatient hospitalization for UTIs caused by ESBL-producing organisms. METHODS: We retrospectively identified infants who were treated in the ED from 2013 to 2017 and who had positive urinalyses and urine cultures positive for greater than 50,000 colony-forming unit per milliliter of a single ESBL-producing urinary pathogen. We abstracted details of clinical management and known previous risk factors, including prior neonatal intensive care unit hospitalization stay, prior UTI caused by an ESBL-producing organism, and known urologic abnormalities. RESULTS: Forty-five UTIs caused by ESBL-producing organisms occurred in 43 patients (mean age of 5.9 months and 59% female)-ESBL Escherichia coli represented the majority (42/45). The incidence of UTIs caused by ESBL-producing organisms ranged from 0.9% to 4.5% during the 5-year study period. The 13 patients (26%) admitted from the ED were significantly younger than discharged patients (1.9 vs 6.7 months, P = 0.016) and more likely to have had prior neonatal intensive care unit hospitalizations (50% vs 15.6%, P = 0.0456). Of the 33 visits (77%) resulting in initial outpatient management, 5 were followed by readmission for parenteral antibiotic treatment. Of those who were readmitted, 40% (n = 2) were afebrile at the time of admission. The remainder (28/33) completed outpatient oral antibiotic courses guided by susceptibilities. Two patients (4%) had negative repeat urine cultures despite in vitro resistance to initial antibiotic coverage. CONCLUSIONS: Extended spectrum ß-lactamase-producing organisms are an increasing cause of UTIs in infants presenting at a pediatric ED, and outpatient management may be reasonable for infants older than 2 months.

Seated Position Does Not Change Lumbar Dimensions Compared With Lateral Position.

OBJECTIVE: The infant lumbar puncture (LP) can be a technically challenging procedure. Understanding the anatomical lumbar dimensions may optimize LP conditions. Data from preterm neonates, older children, and adults indicate measurements of the lumbar spine in the seated LP position may be superior when compared with the lateral position. We use point-of-care ultrasound (US) to determine if the seated position, when compared with the lateral decubitus position, significantly affected the lumbar dimensions of infants 12 months or younger presenting to the pediatric emergency department. METHODS: We conducted a prospective observational study of a convenience sample of patients 12 months or younger. We used US to obtain 3 still images oriented longitudinally in the midline over the L3 to L4 interspace in the lateral decubitus and seated positions. A US fellowship-trained emergency physician, blinded to patient position, measured interspinous space, subarachnoid space width, and spinal canal depth. We then compared the means of all 3 dimensions in the lateral and seated positions. RESULTS: From 50 subjects, 49 subjects provided 46 evaluable sets of images for each measure. Interspinous space, spinal canal depth, and subarachnoid space width did not differ significantly between positions. Mean differences did not exceed 0.02 cm for any of the measured dimensions. We report no significant differences in the 3 lumbar dimensions at the seated position when compared with the lateral decubitus position. CONCLUSIONS: For infants younger than 12 months, sonographic measurements of lumbar dimensions did not differ between the positions commonly used for LP.

Tablet Computer as a Distraction Tool During Facial Laceration Repair: A Randomized Trial.

OBJECTIVES: Child life interventions reduce the anxiety of medical procedures but are not always available in emergency departments. In this study, we determined the effect of parent-directed tablet computer use without child life direction on patient anxiety and on parent and suturing clinician experience during pediatric facial laceration repair. METHODS: In a children's hospital emergency department, we enrolled children 2 to 12 years of age undergoing unsedated facial laceration repairs and randomized them to parent-directed tablet computer distraction or standard supportive care. We measured anxiety using the Observational Scale of Behavioral Distress-Revised (OSBD-R) for 5 procedure phases from videotaped laceration repairs. We compared OSBD-R scores for 5 phases and weighted averages between the tablet and standard care groups. Parents and suturing clinicians completed surveys about their experiences after the procedures. RESULTS: From April 2014 to July 2015, 77 patients (39 tablet, 38 standard) underwent repairs. Age, use of restraint, procedure duration, and number of sutures were similar between the 2 groups. The groups did not differ in procedure phase or weighted-average OSBD-R scores. Parents in the tablet group reported less personal anxiety compared with parents in the standard group (P = 0.01). In a post hoc subgroup analysis, subjects in the unrestrained tablet group had lower OSBD-R scores during the anesthetic injection phase than did subjects in the unrestrained standard group (P = 0.04). If restrained, subjects in the tablet group had higher OSBD-R scores during the anesthetic injection phase than did subjects in the standard group (P = 0.048). CONCLUSIONS: Unrestrained children may benefit from parent-directed tablet computer distraction. Parents who operate the device are less anxious during their children's procedures.

High-Throughput Screening of Kawasaki Disease Sera for Antiviral Antibodies.

Clinical features of Kawasaki disease (KD) display overlap with common pediatric viral illnesses, leading some to hypothesize that a viral infection is the inciting event for KD. To investigate viral infection history in KD patients, we performed comprehensive serological profiling using a high-throughput phage immunoprecipitation sequencing assay covering the complete reference protein sequences of known viruses with human tropism. KD and matched febrile control sera did not demonstrate differences in antiviral antibody profiles. We conclude that in the acute and subacute phases of disease, KD patients do not exhibit serologic evidence of exposure to known viruses that differs from controls.

Predicting Hemolytic Uremic Syndrome and Renal Replacement Therapy in Shiga Toxin-producing Escherichia coli-infected Children.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care. METHODS: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children aged <18 years who submitted STEC-positive specimens between January 2011 and December 2015 at a participating study institution were eligible. RESULTS: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age (0.77 [.69-.85] per year), leukocyte count ≥13.0 × 103/µL (2.54 [1.42-4.54]), higher hematocrit (1.83 [1.21-2.77] per 5% increase) and serum creatinine (10.82 [1.49-78.69] per 1 mg/dL increase), platelet count <250 × 103/µL (1.92 [1.02-3.60]), lower serum sodium (1.12 [1.02-1.23 per 1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50 [1.14-5.46]). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (OR, 0.70 [95% CI, .54-.90]). RRT predictors (all shown as OR [95% CI]) included female sex (2.27 [1.14-4.50]), younger age (0.83 [.74-.92] per year), lower serum sodium (1.15 [1.04-1.27] per mmol/L decrease), higher leukocyte count ≥13.0 × 103/µL (2.35 [1.17-4.72]) and creatinine (7.75 [1.20-50.16] per 1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71 [1.18-6.21]). CONCLUSIONS: The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring.

Bilateral tibial tubercle avulsion fractures: A pediatric orthopedic injury at high risk for compartment syndrome.

Adolescent tibial tubercle avulsion fractures represent an uncommon, but clinically significant condition for emergency medicine physicians. Early recognition of the signs and symptoms of this pediatric orthopedic diagnosis are important, as anterior compartment syndrome can occur in up to 10-20% of cases. Anterior tibial tubercle fractures are generally sport related injuries, occurring primarily in otherwise healthy adolescent males between the ages of 11-17. They account for less than 3% of all epiphyseal injuries in this age group and are rarely bilateral in nature. In this article, we present a case with two unique clinical features: bilateral sports related tibial tubercle avulsion fractures and subsequent development of bilateral clinical compartment syndrome. We briefly review the risk factors, presentation, and diagnosis of this rare but clinically important condition.

Comparison of pediatric post-reduction fluoroscopic- and ultrasound forearm fracture images.

OBJECTIVE: Emergency department (ED) reduction of pediatric fractures occurs most commonly in the forearm and can be challenging if fluoroscopy is not available. We sought to assess the ability of point of-care ultrasonography (POCUS) to predict adequacy of reduction by fluoroscopy. METHODS: We prospectively enrolled ED patients 0-17 years of age with radial and/or ulnar fractures requiring reduction under fluoroscopic guidance. Post-reduction POCUS (probe dorsal, volar, and coronal) and fluoroscopic (AP and lateral) fracture images were recorded. Fracture angles were compared between blinded POCUS and fluoroscopic measurements and between POCUS measurements by a blinded emergency physician and a blinded radiologist, reporting mean differences and 95% confidence intervals. We calculated sensitivity, specificity, and likelihood ratios of POCUS in the prediction of fluoroscopically detected post-reduction malalignment, as interpreted by a blinded pediatric orthopaedist. RESULTS: The 58 patients were 7.9 ±â€¯3.5 years of age and had 21 radial (36%), 1 ulnar (2%), and 36 radioulnar (62%) fractures. Fluoroscopy and POCUS angles were within a mean of 0.1°-3.2°, depending on the site and surface measured. Radiologist- and emergency physician-interpreted POCUS measurements were within a mean of 1° in all dimensions. POCUS identified inadequate reductions with 100% sensitivity and 92-93% specificity. CONCLUSIONS: Blinded emergency medicine and radiology interpretations of post-reduction POCUS fracture images agree closely. Post-reduction POCUS measurements are comparable to those obtained by fluoroscopy and accurately predict adequacy of reduction. POCUS can be used to guide pediatric fracture reduction when bedside fluoroscopy is not available in the ED.

Kawasaki Disease Outcomes and Response to Therapy in a Multiethnic Community: A 10-Year Experience.

OBJECTIVES: To describe the epidemiology, response to therapy, and outcomes of Kawasaki disease in a multiethnic community with a large Hispanic and Asian population. STUDY DESIGN: We analyzed prospectively collected data from 788 unselected patients with Kawasaki disease diagnosed and treated at a single medical center over a 10-year period. RESULTS: The average incidence of Kawasaki disease in children <5 years in San Diego County over the 10 years from 2006 to 2015 was 25 per 100 000 children, with the greatest incidence (50 per 100 000) for Asian/Pacific Islanders. Compared with other race/ethnicities, Asian/Pacific Islander patients with Kawasaki disease were younger, were diagnosed earlier in the course of their fever, had higher levels of inflammatory markers, and were more likely to develop aneurysms. There was no difference across race/ethnicity groups in response to intravenous immunoglobulin therapy. Filipino children had the highest recurrence rates (9.1%; 95% CI, 3.0%-22.6%) and 12 of 788 patients (1.5%) had a first- or second-degree relative with a history of Kawasaki disease. After correcting for age of onset, sex, and illness day at diagnosis, Asian/Pacific Islander children had an increased risk of developing aneurysms (aOR, 2.37; 95% CI, 1.37-4.11; P = .002). Overall, 180 of 788 patients (22.8%) had a maximal Z score of 2.5-10.0 and 14 of the 788 patients (1.8%) had a maximal Z score ≥10.0 despite 84% of these patients being treated within 10 days of fever onset. CONCLUSIONS: Our data provide new insights into the natural history of treated Kawasaki disease in a multiethnic population. Patient race/ethnicity influenced susceptibility to Kawasaki disease, timing of diagnosis, coronary artery outcome, and recurrence rates.

A Classification Tool for Differentiation of Kawasaki Disease from Other Febrile Illnesses.

OBJECTIVE: To develop and validate a novel decision tree-based clinical algorithm to differentiate Kawasaki disease (KD) from other pediatric febrile illnesses that share common clinical characteristics. STUDY DESIGN: Using clinical and laboratory data from 801 subjects with acute KD (533 for development, and 268 for validation) and 479 febrile control subjects (318 for development, and 161 for validation), we developed a stepwise KD diagnostic algorithm combining our previously developed linear discriminant analysis (LDA)-based model with a newly developed tree-based algorithm. RESULTS: The primary model (LDA) stratified the 1280 subjects into febrile controls (n = 276), indeterminate (n = 247), and KD (n = 757) subgroups. The subsequent model (decision trees) further classified the indeterminate group into febrile controls (n = 103) and KD (n = 58) subgroups, leaving only 29 of 801 KD (3.6%) and 57 of 479 febrile control (11.9%) subjects indeterminate. The 2-step algorithm had a sensitivity of 96.0% and a specificity of 78.5%, and correctly classified all subjects with KD who later developed coronary artery aneurysms. CONCLUSION: The addition of a decision tree step increased sensitivity and specificity in the classification of subject with KD and febrile controls over our previously described LDA model. A multicenter trial is needed to prospectively determine its utility as a point of care diagnostic test for KD.

The Prevalence of Bruising Among Infants in Pediatric Emergency Departments.

STUDY OBJECTIVE: Bruising can indicate abuse for infants. Bruise prevalence among infants in the pediatric emergency department (ED) setting is unknown. Our objective is to determine prevalence of bruising, associated chief complaints, and frequency of abuse evaluations in previously healthy infants presenting to pediatric EDs. METHODS: We conducted a prospective, observational, multicenter study of infants aged 12 months or younger presenting to pediatric EDs. Structured sampling was used. Pediatric emergency medicine clinicians performed complete skin examinations to screen for bruising. Study investigators documented skin findings, date of visit, patient's age, chief complaint, and abuse evaluation. The primary outcome was prevalence of bruising. Secondary outcomes were prevalence of bruising based on chief complaint and frequency of abuse evaluation. Point estimates of bruise prevalence and differences in bruise prevalence between patient subgroups were calculated with 95% confidence intervals (CIs). RESULTS: Bruising was identified in 88 of 2,488 infants (3.5%; 95% CI 2.9% to 4.4%). Rates of bruising for infants 5 months and younger and older than 5 months were 1.3% and 6.4%, respectively (difference 5.1%; 95% CI 3.6% to 6.8%). For infants 5 months and younger, 83% of bruising was associated with a trauma chief complaint and only 0.2% of infants presenting with a medical chief complaint had bruising. Pediatric emergency medicine clinicians obtained abuse evaluations on 23% of infants with bruising, and that rate increased to 50% for infants 5 months and younger. CONCLUSION: Bruising prevalence in children 12 months and younger who were evaluated in pediatric EDs was low, increased within age strata, and was most often associated with a trauma chief complaint. Most bruised infants did not undergo an abuse evaluation.

Differences in GlycA and lipoprotein particle parameters may help distinguish acute kawasaki disease from other febrile illnesses in children.

BACKGROUND: Glycosylation patterns of serum proteins, such as α1-acid glycoprotein, are modified during an acute phase reaction. The response of acute Kawasaki disease (KD) patients to IVIG treatment has been linked to sialic acid levels on native IgG, suggesting that protein glycosylation patterns vary during the immune response in acute KD. Additionally, the distribution and function of lipoprotein particles are altered during inflammation. Therefore, the aim of this study was to explore the potential for GlycA, a marker of protein glycosylation, and the lipoprotein particle profile to distinguish pediatric patients with acute KD from those with other febrile illnesses. METHODS: Nuclear magnetic resonance was used to quantify GlycA and lipoprotein particle classes and subclasses in pediatric subjects with acute KD (n = 75), post-treatment subacute (n = 36) and convalescent (n = 63) KD, as well as febrile controls (n = 48), and age-similar healthy controls (n = 48). RESULTS: GlycA was elevated in acute KD subjects compared to febrile controls with bacterial or viral infections, IVIG-treated subacute and convalescent KD subjects, and healthy children (P <0.0001). Acute KD subjects had increased total and small low density lipoprotein particle numbers (LDL-P) (P <0.0001) and decreased total high density lipoprotein particle number (HDL-P) (P <0.0001) compared to febrile controls. Consequently, the ratio of LDL-P to HDL-P was higher in acute KD subjects than all groups tested (P <0.0001). While GlycA, CRP, erythrocyte sedimentation rate, LDL-P and LDL-P/HDL-P ratio were able to distinguish patients with KD from those with other febrile illnesses (AUC = 0.789-0.884), the combinations of GlycA and LDL-P (AUC = 0.909) or GlycA and the LDL-P/HDL-P ratio (AUC = 0.910) were best at discerning KD in patients 6-10 days after illness onset. CONCLUSIONS: High levels of GlycA confirm enhanced protein glycosylation as part of the acute phase response in KD patients. When combined with common laboratory tests and clinical characteristics, GlycA and NMR-measured lipoprotein particle parameters may be useful for distinguishing acute KD from bacterial or viral illnesses in pediatric patients.

Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children.

IMPORTANCE: Because clinical features do not reliably distinguish bacterial from viral infection, many children worldwide receive unnecessary antibiotic treatment, while bacterial infection is missed in others. OBJECTIVE: To identify a blood RNA expression signature that distinguishes bacterial from viral infection in febrile children. DESIGN, SETTING, AND PARTICIPANTS: Febrile children presenting to participating hospitals in the United Kingdom, Spain, the Netherlands, and the United States between 2009-2013 were prospectively recruited, comprising a discovery group and validation group. Each group was classified after microbiological investigation as having definite bacterial infection, definite viral infection, or indeterminate infection. RNA expression signatures distinguishing definite bacterial from viral infection were identified in the discovery group and diagnostic performance assessed in the validation group. Additional validation was undertaken in separate studies of children with meningococcal disease (n = 24) and inflammatory diseases (n = 48) and on published gene expression datasets. EXPOSURES: A 2-transcript RNA expression signature distinguishing bacterial infection from viral infection was evaluated against clinical and microbiological diagnosis. MAIN OUTCOMES AND MEASURES: Definite bacterial and viral infection was confirmed by culture or molecular detection of the pathogens. Performance of the RNA signature was evaluated in the definite bacterial and viral group and in the indeterminate infection group. RESULTS: The discovery group of 240 children (median age, 19 months; 62% male) included 52 with definite bacterial infection, of whom 36 (69%) required intensive care, and 92 with definite viral infection, of whom 32 (35%) required intensive care. Ninety-six children had indeterminate infection. Analysis of RNA expression data identified a 38-transcript signature distinguishing bacterial from viral infection. A smaller (2-transcript) signature (FAM89A and IFI44L) was identified by removing highly correlated transcripts. When this 2-transcript signature was implemented as a disease risk score in the validation group (130 children, with 23 definite bacterial, 28 definite viral, and 79 indeterminate infections; median age, 17 months; 57% male), all 23 patients with microbiologically confirmed definite bacterial infection were classified as bacterial (sensitivity, 100% [95% CI, 100%-100%]) and 27 of 28 patients with definite viral infection were classified as viral (specificity, 96.4% [95% CI, 89.3%-100%]). When applied to additional validation datasets from patients with meningococcal and inflammatory diseases, bacterial infection was identified with a sensitivity of 91.7% (95% CI, 79.2%-100%) and 90.0% (95% CI, 70.0%-100%), respectively, and with specificity of 96.0% (95% CI, 88.0%-100%) and 95.8% (95% CI, 89.6%-100%). Of the children in the indeterminate groups, 46.3% (63/136) were classified as having bacterial infection, although 94.9% (129/136) received antibiotic treatment. CONCLUSIONS AND RELEVANCE: This study provides preliminary data regarding test accuracy of a 2-transcript host RNA signature discriminating bacterial from viral infection in febrile children. Further studies are needed in diverse groups of patients to assess accuracy and clinical utility of this test in different clinical settings.

Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial.

BACKGROUND: Kawasaki disease, the most common cause of acquired heart disease in developed countries, is a self-limited vasculitis that is treated with high doses of intravenous immunoglobulin. Resistance to intravenous immunoglobulin in Kawasaki disease increases the risk of coronary artery aneurysms. We assessed whether the addition of infliximab to standard therapy (intravenous immunoglobulin and aspirin) in acute Kawasaki disease reduces the rate of treatment resistance. METHODS: We undertook a phase 3, randomised, double-blind, placebo-controlled trial in two children's hospitals in the USA to assess the addition of infliximab (5 mg per kg) to standard therapy. Eligible participants were children aged 4 weeks-17 years who had a fever (temperature ≥38·0°C) for 3-10 days and met American Heart Association criteria for Kawasaki disease. Participants were randomly allocated in 1:1 ratio to two treatment groups: infliximab 5 mg/kg at 1 mg/mL intravenously over 2 h or placebo (normal saline 5 mL/kg, administered intravenously). Randomisation was based on a randomly permuted block design (block sizes 2 and 4), stratified by age, sex, and centre. Patients, treating physicians and staff, study team members, and echocardiographers were all masked to treament assignment. The primary outcome was the difference between the groups in treatment resistance defined as a temperature of 38·0°C or higher at 36 h to 7 days after completion of the infusion of intravenous immunoglobulin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00760435. FINDINGS: 196 patients were enrolled and randomised: 98 to the infliximab group and 98 to placebo. One patient in the placebo group was withdrawn from the study because of hypotension before receiving treatment. Treatment resistance rate did not differ significantly (11 [11·2%] for infliximab and 11 [11·3%] for placebo; p=0·81). Compared with the placebo group, participants given infliximab had fewer days of fever (median 1 day for infliximab vs 2 days for placebo; p<0·0001). At week 2, infliximab-treated patients had greater mean reductions in erythrocyte sedimentation rate (p=0·009) and a two-fold greater decrease in Z score of the left anterior descending artery (p=0·045) than did those in the placebo group, but this difference was not significant at week 5. Participants in the infliximab group had a greater mean reduction in C-reactive protein concentration (p=0·0003) and in absolute neutrophil count (p=0·024) at 24 h after treatment than did those given placebo, but by week 2 this difference was not significant. At week 5, none of the laboratory values differed significantly compared with baseline. No significant differences were recorded between the two groups at any timepoint in proximal right coronary artery Z scores, age-adjusted haemoglobin values, duration of hospital stay, or any other laboratory markers of inflammation measured. No reactions to intravenous immunoglobulin infusion occurred in patients treated with infliximab compared with 13 (13·4%) patients given placebo (p<0·0001). No serious adverse events were directly attributable to infliximab infusion. INTERPRETATION: The addition of infliximab to primary treatment in acute Kawasaki disease did not reduce treatment resistance. However, it was safe and well tolerated and reduced fever duration, some markers of inflammation, left anterior descending coronary artery Z score, and intravenous immunoglobulin reaction rates. FUNDING: US Food and Drug Administration, Robert Wood Johnson Foundation, and Janssen Biotech.

Novel data-mining approach identifies biomarkers for diagnosis of Kawasaki disease.

BACKGROUND: As Kawasaki disease (KD) shares many clinical features with other more common febrile illnesses and misdiagnosis, leading to a delay in treatment, increases the risk of coronary artery damage, a diagnostic test for KD is urgently needed. We sought to develop a panel of biomarkers that could distinguish between acute KD patients and febrile controls (FC) with sufficient accuracy to be clinically useful. METHODS: Plasma samples were collected from three independent cohorts of FC and acute KD patients who met the American Heart Association definition for KD and presented within the first 10 d of fever. The levels of 88 biomarkers associated with inflammation were assessed by Luminex bead technology. Unsupervised clustering followed by supervised clustering using a Random Forest model was used to find a panel of candidate biomarkers. RESULTS: A panel of biomarkers commonly available in the hospital laboratory (absolute neutrophil count, erythrocyte sedimentation rate, alanine aminotransferase, γ-glutamyl transferase, concentrations of α-1-antitrypsin, C-reactive protein, and fibrinogen, and platelet count) accurately diagnosed 81-96% of KD patients in a series of three independent cohorts. CONCLUSION: After prospective validation, this eight-biomarker panel may improve the recognition of KD.

Inpatient Treatment after Multi-Dose Racemic Epinephrine for Croup in the Emergency Department.

BACKGROUND: Emergency department (ED) discharge is safe when croup-related stridor has resolved after corticosteroids and a single dose of racemic epinephrine (RE). Little evidence supports the traditional practice of hospital admission after ≥ 2 doses of RE. OBJECTIVE: Our aim was to describe the frequency and timing of clinically important inpatient interventions after ≥ 2 ED RE doses. METHODS: We identified patients hospitalized for croup after ED treatment with corticosteroids and ≥2 doses of RE. We compared asymptomatic (admitted solely on the number of RE doses) and symptomatic (admitted due to disease severity) groups with regard to inpatient RE administration, supplemental oxygen, helium-oxygen mixture (heliox) therapy, intubation, or transfer to a higher level of care, time to hospital discharge, and revisit and readmission rates within 48 h of discharge. RESULTS: Of 200 subjects admitted after ≥ 2 ED RE doses, 72 (36%) received clinically important inpatient interventions: RE (n = 68 [34%]), heliox (n = 9 [5%]), and supplemental oxygen (n = 4 [2%]). Of patients who received inpatient RE, 53% received only 1 dose. No patients underwent intubation or transfer to higher level of care. The 112 asymptomatic patients had fewer interventions (14% vs. 63%; p < 0.001) and shorter hospital durations (14.5 vs. 22 h; p < 0.001). Only 14% of the asymptomatic group received RE, with 75% receiving a single dose. There were no differences in revisit and readmission rates. CONCLUSIONS: Inpatient interventions after ≥ 2 ED doses of RE for croup were infrequent, most commonly RE administration. Most patients asymptomatic upon admission require 0-1 inpatient RE doses and may be candidates for outpatient management.

Point-of-care differentiation of Kawasaki disease from other febrile illnesses.

OBJECTIVE: To test whether statistical learning on clinical and laboratory test patterns would lead to an algorithm for Kawasaki disease (KD) diagnosis that could aid clinicians. STUDY DESIGN: Demographic, clinical, and laboratory data were prospectively collected for subjects with KD and febrile controls (FCs) using a standardized data collection form. RESULTS: Our multivariate models were trained with a cohort of 276 patients with KD and 243 FCs (who shared some features of KD) and validated with a cohort of 136 patients with KD and 121 FCs using either clinical data, laboratory test results, or their combination. Our KD scoring method stratified the subjects into subgroups with low (FC diagnosis, negative predictive value >95%), intermediate, and high (KD diagnosis, positive predictive value >95%) scores. Combining both clinical and laboratory test results, the algorithm diagnosed 81.2% of all training and 74.3% of all testing of patients with KD in the high score group and 67.5% of all training and 62.8% of all testing FCs in the low score group. CONCLUSIONS: Our KD scoring metric and the associated data system with online (http://translationalmedicine.stanford.edu/cgi-bin/KD/kd.pl) and smartphone applications are easily accessible, inexpensive tools to improve the differentiation of most children with KD from FCs with other pediatric illnesses.

Lymph-node-first presentation of Kawasaki disease compared with bacterial cervical adenitis and typical Kawasaki disease.

OBJECTIVE: To identify characteristics differentiating the node-first presentation of Kawasaki disease (NFKD) from bacterial cervical lymphadenitis (BCL) and typical Kawasaki disease (KD). STUDY DESIGN: From our prospectively collected database, we compared clinical, laboratory, and imaging characteristics of NFKD and BCL cohorts and performed multivariable logistic regression to identify variables that distinguish NFKD from BCL. We then compared outcomes of patients with NFKD and patients with typical KD treated during the same period. RESULTS: Over 7 years, 57 patients were hospitalized for NFKD, 78 for BCL, and 287 for typical KD. Patients with NFKD were older and had more medical encounters and longer duration of illness before the correct diagnosis was made than did patients with BCL. Of patients with NFKD, 33% had an admission diagnosis of bacterial adenitis or abscess. Compared with patients with BCL, patients with NFKD had lower leukocyte (white blood cell), hemoglobin, and platelet counts and higher absolute band counts (ABCs), C-reactive protein (CRP), alanine transaminase and γ-glutamyl transpeptidase levels, and erythrocyte sedimentation rates. In the multivariable analysis, smaller nodes, lower white blood cell count, and higher ABC and CRP were independently associated with NFKD. Patients with NFKD had multiple enlarged solid nodes and comparable rates of retropharyngeal edema. Compared with patients with typical KD, patients with NFKD were older, had more severe inflammation, and had similar rates of coronary artery abnormalities and resistance to intravenous immune globulin. CONCLUSIONS: High ABC and CRP values and multiple enlarged solid nodes in febrile patients with cervical adenopathy should prompt consideration of NFKD to prevent delayed diagnosis of KD. Retropharyngeal edema on radiography should not dissuade from the diagnosis of NFKD.

A Deep Learning Framework for Image-Based Screening of Kawasaki Disease.

Kawasaki disease (KD) is a leading cause of acquired heart disease in children and is characterized by the presence of a combination of five clinical signs assessed during the physical examination. Timely treatment of intravenous immunoglobin is needed to prevent coronary artery aneurysm formation, but KD is usually diagnosed when pediatric patients are evaluated by a clinician in the emergency department days after onset. One or more of the five clinical signs usually manifests in pediatric patients prior to ED admission, presenting an opportunity for earlier intervention if families receive guidance to seek medical care as soon as clinical signs are observed along with a fever for at least five days. We present a deep learning framework for a novel screening tool to calculate the relative risk of KD by analyzing images of the five clinical signs. The framework consists of convolutional neural networks to separately calculate the risk for each clinical sign, and a new algorithm to determine what clinical sign is in an image. We achieved a mean accuracy of 90% during 10-fold cross-validation and 88% during external validation for the new algorithm. These results demonstrate the algorithms in the proposed screening tool can be utilized by families to determine if their child should be evaluated by a clinician based on the number of clinical signs consistent with KD.Clinical Relevance- This screening framework has the potential for earlier clinical evaluation and detection of KD to reduce the risk of coronary artery complications.