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.

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.

Single center blind testing of a US multi-center validated diagnostic algorithm for Kawasaki disease in Taiwan.

Background: Kawasaki disease (KD) is the leading cause of acquired heart disease in children. The major challenge in KD diagnosis is that it shares clinical signs with other childhood febrile control (FC) subjects. We sought to determine if our algorithmic approach applied to a Taiwan cohort. Methods: A single center (Chang Gung Memorial Hospital in Taiwan) cohort of patients suspected with acute KD were prospectively enrolled by local KD specialists for KD analysis. Our previously single-center developed computer-based two-step algorithm was further tested by a five-center validation in US. This first blinded multi-center trial validated our approach, with sufficient sensitivity and positive predictive value, to identify most patients with KD diagnosed at centers across the US. This study involved 418 KDs and 259 FCs from the Chang Gung Memorial Hospital in Taiwan. Findings: Our diagnostic algorithm retained sensitivity (379 of 418; 90.7%), specificity (223 of 259; 86.1%), PPV (379 of 409; 92.7%), and NPV (223 of 247; 90.3%) comparable to previous US 2016 single center and US 2020 fiver center results. Only 4.7% (15 of 418) of KD and 2.3% (6 of 259) of FC patients were identified as indeterminate. The algorithm identified 18 of 50 (36%) KD patients who presented 2 or 3 principal criteria. Of 418 KD patients, 157 were infants younger than one year and 89.2% (140 of 157) were classified correctly. Of the 44 patients with KD who had coronary artery abnormalities, our diagnostic algorithm correctly identified 43 (97.7%) including all patients with dilated coronary artery but one who found to resolve in 8 weeks. Interpretation: This work demonstrates the applicability of our algorithmic approach and diagnostic portability in Taiwan.

A machine-learning algorithm for diagnosis of multisystem inflammatory syndrome in children and Kawasaki disease in the USA: a retrospective model development and validation study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a novel disease that was identified during the COVID-19 pandemic and is characterised by systemic inflammation following SARS-CoV-2 infection. Early detection of MIS-C is a challenge given its clinical similarities to Kawasaki disease and other acute febrile childhood illnesses. We aimed to develop and validate an artificial intelligence algorithm that can distinguish among MIS-C, Kawasaki disease, and other similar febrile illnesses and aid in the diagnosis of patients in the emergency department and acute care setting. METHODS: In this retrospective model development and validation study, we developed a deep-learning algorithm called KIDMATCH (Kawasaki Disease vs Multisystem Inflammatory Syndrome in Children) using patient age, the five classic clinical Kawasaki disease signs, and 17 laboratory measurements. All features were prospectively collected at the time of initial evaluation from patients diagnosed with Kawasaki disease or other febrile illness between Jan 1, 2009, and Dec 31, 2019, at Rady Children's Hospital in San Diego (CA, USA). For patients with MIS-C, the same data were collected from patients between May 7, 2020, and July 20, 2021, at Rady Children's Hospital, Connecticut Children's Medical Center in Hartford (CT, USA), and Children's Hospital Los Angeles (CA, USA). We trained a two-stage model consisting of feedforward neural networks to distinguish between patients with MIS-C and those without and then those with Kawasaki disease and other febrile illnesses. After internally validating the algorithm using stratified tenfold cross-validation, we incorporated a conformal prediction framework to tag patients with erroneous data or distribution shifts. We finally externally validated KIDMATCH on patients with MIS-C enrolled between April 22, 2020, and July 21, 2021, from Boston Children's Hospital (MA, USA), Children's National Hospital (Washington, DC, USA), and the CHARMS Study Group consortium of 14 US hospitals. FINDINGS: 1517 patients diagnosed at Rady Children's Hospital between Jan 1, 2009, and June 7, 2021, with MIS-C (n=69), Kawasaki disease (n=775), or other febrile illnesses (n=673) were identified for internal validation, with an additional 16 patients with MIS-C included from Connecticut Children's Medical Center and 50 from Children's Hospital Los Angeles between May 7, 2020, and July 20, 2021. KIDMATCH achieved a median area under the receiver operating characteristic curve during internal validation of 98·8% (IQR 98·0-99·3) in the first stage and 96·0% (95·6-97·2) in the second stage. We externally validated KIDMATCH on 175 patients with MIS-C from Boston Children's Hospital (n=50), Children's National Hospital (n=42), and the CHARMS Study Group consortium of 14 US hospitals (n=83). External validation of KIDMATCH on patients with MIS-C correctly classified 76 of 81 patients (94% accuracy, two rejected by conformal prediction) from 14 hospitals in the CHARMS Study Group consortium, 47 of 49 patients (96% accuracy, one rejected by conformal prediction) from Boston Children's Hospital, and 36 of 40 patients (90% accuracy, two rejected by conformal prediction) from Children's National Hospital. INTERPRETATION: KIDMATCH has the potential to aid front-line clinicians to distinguish between MIS-C, Kawasaki disease, and other similar febrile illnesses to allow prompt treatment and prevent severe complications. FUNDING: US Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Heart, Lung, and Blood Institute, US Patient-Centered Outcomes Research Institute, US National Library of Medicine, the McCance Foundation, and the Gordon and Marilyn Macklin Foundation.

An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease.

Multisystem inflammatory syndrome in children (MIS-C) is an illness that emerged amidst the COVID-19 pandemic but shares many clinical features with the pre-pandemic syndrome of Kawasaki disease (KD). Here we compare the two syndromes using a computational toolbox of two gene signatures that were developed in the context of SARS-CoV-2 infection, i.e., the viral pandemic (ViP) and severe-ViP signatures and a 13-transcript signature previously demonstrated to be diagnostic for KD, and validated our findings in whole blood RNA sequences, serum cytokines, and formalin fixed heart tissues. Results show that KD and MIS-C are on the same continuum of the host immune response as COVID-19. Both the pediatric syndromes converge upon an IL15/IL15RA-centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis; however, they diverge in other laboratory parameters and cardiac phenotypes. The ViP signatures reveal unique targetable cytokine pathways in MIS-C, place MIS-C farther along in the spectrum in severity compared to KD and pinpoint key clinical (reduced cardiac function) and laboratory (thrombocytopenia and eosinopenia) parameters that can be useful to monitor severity.

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.

Multicenter Validation of a Machine Learning Algorithm for Diagnosing Pediatric Patients with Multisystem Inflammatory Syndrome and Kawasaki Disease.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a novel disease identified during the COVID-19 pandemic characterized by systemic inflammation following SARS-CoV-2 infection. Delays in diagnosing MIS-C may lead to more severe disease with cardiac dysfunction or death. Most pediatric patients recover fully with anti-inflammatory treatments, but early detection of MIS-C remains a challenge given its clinical similarities to Kawasaki disease (KD) and other acute childhood illnesses. METHODS: We developed KIDMATCH ( K awasak I D isease vs M ultisystem Infl A mma T ory syndrome in CH ildren), a deep learning algorithm for screening patients for MIS-C, KD, or other febrile illness, using age, the five classical clinical KD signs, and 17 laboratory measurements prospectively collected within 24 hours of admission to the emergency department from 1448 patients diagnosed with KD or other febrile illness between January 1, 2009 and December 31, 2019 at Rady Children's Hospital. For MIS-C patients, the same data was collected from 131 patients between May 14, 2020 to June 18, 2021 at Rady Children's Hospital, Connecticut Children's Hospital, and Children's Hospital Los Angeles. We trained a two-stage model consisting of feedforward neural networks to distinguish between MIS-C and non MIS-C patients and then KD and other febrile illness. After internally validating the algorithm using 10-fold cross validation, we incorporated a conformal prediction framework to tag patients with erroneous data or distribution shifts, enhancing the model generalizability and confidence by flagging unfamiliar cases as indeterminate instead of making spurious predictions. We externally validated KIDMATCH on 175 MIS-C patients from 16 hospitals across the United States. FINDINGS: KIDMATCH achieved a high median area under the curve in the 10-fold cross validation of 0.988 [IQR: 0.98-0.993] in the first stage and 0.96 [IQR: 0.956-0.972] in the second stage using thresholds set at 95% sensitivity to detect positive MIS-C and KD cases respectively during training. External validation of KIDMATCH on MIS-C patients correctly classified 76/83 (2 rejected) patients from the CHARMS consortium, 47/50 (1 rejected) patients from Boston Children's Hospital, and 36/42 (2 rejected) patients from Children's National Hospital. INTERPRETATION: KIDMATCH has the potential to aid frontline clinicians with distinguishing between MIS-C, KD, and similar febrile illnesses in a timely manner to allow prompt treatment and prevent severe complications. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Heart, Lung, and Blood Institute, Patient-Centered Outcomes Research Institute, National Library of Medicine.

Implementation of KIDMATCH: A Clinical Decision Support Tool for Diagnosing Pediatric Patients with Multisystem Inflammatory Syndrome and Kawasaki Disease.

Multisystem inflammatory syndrome in children (MIS-C) is a novel disease identified during the COVID-19 pandemic that may lead to cardiac dysfunction or death in pediatric patients. Early detection of MIS-C remains a challenge given the lack of a diagnostic test and its clinical similarities to Kawasaki disease (KD) and other acute childhood illnesses. We developed and validated the KawasakI Disease vs Multisystem InflAmmaTory syndrome in CHildren (KIDMATCH) clinical decision support tool for screening patients for MIS-C, KD, or other febrile illnesses. Here we describe the implementation and iterative refinement of KIDMATCH with provider feedback as a web calculator in the clinical workflow within Rady Children's Hospital. Our findings demonstrate KIDMATCH and its underlying artificial intelligence model have clinical utility in aiding clinicians at the time of initial evaluation within the hospital setting to distinguish patients who have MIS-C, KD, or other febrile illnesses.

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.

Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C.

BACKGROUNDMultisystem inflammatory syndrome in children (MIS-C) is a rare but potentially severe illness that follows exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Kawasaki disease (KD) shares several clinical features with MIS-C, which prompted the use of intravenous immunoglobulin (IVIG), a mainstay therapy for KD. Both diseases share a robust activation of the innate immune system, including the IL-1 signaling pathway, and IL-1 blockade has been used for the treatment of both MIS-C and KD. The mechanism of action of IVIG in these 2 diseases and the cellular source of IL-1ß have not been defined.METHODSThe effects of IVIG on peripheral blood leukocyte populations from patients with MIS-C and KD were examined using flow cytometry and mass cytometry (CyTOF) and live-cell imaging.RESULTSCirculating neutrophils were highly activated in patients with KD and MIS-C and were a major source of IL-1ß. Following IVIG treatment, activated IL-1ß+ neutrophils were reduced in the circulation. In vitro, IVIG was a potent activator of neutrophil cell death via PI3K and NADPH oxidase, but independently of caspase activation.CONCLUSIONSActivated neutrophils expressing IL-1ß can be targeted by IVIG, supporting its use in both KD and MIS-C to ameliorate inflammation.FUNDINGPatient Centered Outcomes Research Institute; NIH; American Asthma Foundation; American Heart Association; Novo Nordisk Foundation; NIGMS; American Academy of Allergy, Asthma and Immunology Foundation.

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.

Multicentre validation of a computer-based tool for differentiation of acute Kawasaki disease from clinically similar febrile illnesses.

BACKGROUND: The clinical features of Kawasaki disease (KD) overlap with those of other paediatric febrile illnesses. A missed or delayed diagnosis increases the risk of coronary artery damage. Our computer algorithm for KD and febrile illness differentiation had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 94.8%, 70.8%, 93.7% and 98.3%, respectively, in a single-centre validation study. We sought to determine the performance of this algorithm with febrile children from multiple institutions across the USA. METHODS: We used our previously published 18-variable panel that includes illness day, the five KD clinical criteria and readily available laboratory values. We applied this two-step algorithm using a linear discriminant analysis-based clinical model followed by a random forest-based algorithm to a cohort of 1059 acute KD and 282 febrile control patients from five children's hospitals across the USA. RESULTS: The algorithm correctly classified 970 of 1059 patients with KD and 163 of 282 febrile controls resulting in a sensitivity of 91.6%, specificity of 57.8% and PPV and NPV of 95.4% and 93.1%, respectively. The algorithm also correctly identified 218 of the 232 KD patients (94.0%) with abnormal echocardiograms. INTERPRETATION: The expectation is that the predictive accuracy of the algorithm will be reduced in a real-world setting in which patients with KD are rare and febrile controls are common. However, the results of the current analysis suggest that this algorithm warrants a prospective, multicentre study to evaluate its potential utility as a physician support tool.

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.

Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature.

Importance: To date, there is no diagnostic test for Kawasaki disease (KD). Diagnosis is based on clinical features shared with other febrile conditions, frequently resulting in delayed or missed treatment and an increased risk of coronary artery aneurysms. Objective: To identify a whole-blood gene expression signature that distinguishes children with KD in the first week of illness from other febrile conditions. Design, Setting, and Participants: The case-control study comprised a discovery group that included a training and test set and a validation group of children with KD or comparator febrile illness. The setting was pediatric centers in the United Kingdom, Spain, the Netherlands, and the United States. The training and test discovery group comprised 404 children with infectious and inflammatory conditions (78 KD, 84 other inflammatory diseases, and 242 bacterial or viral infections) and 55 healthy controls. The independent validation group comprised 102 patients with KD, including 72 in the first 7 days of illness, and 130 febrile controls. The study dates were March 1, 2009, to November 14, 2013, and data analysis took place from January 1, 2015, to December 31, 2017. Main Outcomes and Measures: Whole-blood gene expression was evaluated using microarrays, and minimal transcript sets distinguishing KD were identified using a novel variable selection method (parallel regularized regression model search). The ability of transcript signatures (implemented as disease risk scores) to discriminate KD cases from controls was assessed by area under the curve (AUC), sensitivity, and specificity at the optimal cut point according to the Youden index. Results: Among 404 patients in the discovery set, there were 78 with KD (median age, 27 months; 55.1% male) and 326 febrile controls (median age, 37 months; 56.4% male). Among 202 patients in the validation set, there were 72 with KD (median age, 34 months; 62.5% male) and 130 febrile controls (median age, 17 months; 56.9% male). A 13-transcript signature identified in the discovery training set distinguished KD from other infectious and inflammatory conditions in the discovery test set, with AUC of 96.2% (95% CI, 92.5%-99.9%), sensitivity of 81.7% (95% CI, 60.0%-94.8%), and specificity of 92.1% (95% CI, 84.0%-97.0%). In the validation set, the signature distinguished KD from febrile controls, with AUC of 94.6% (95% CI, 91.3%-98.0%), sensitivity of 85.9% (95% CI, 76.8%-92.6%), and specificity of 89.1% (95% CI, 83.0%-93.7%). The signature was applied to clinically defined categories of definite, highly probable, and possible KD, resulting in AUCs of 98.1% (95% CI, 94.5%-100%), 96.3% (95% CI, 93.3%-99.4%), and 70.0% (95% CI, 53.4%-86.6%), respectively, mirroring certainty of clinical diagnosis. Conclusions and Relevance: In this study, a 13-transcript blood gene expression signature distinguished KD from other febrile conditions. Diagnostic accuracy increased with certainty of clinical diagnosis. A test incorporating the 13-transcript disease risk score may enable earlier diagnosis and treatment of KD and reduce inappropriate treatment in those with other diagnoses.