Clinical implications of gallbladder enlargement in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) presents with gallbladder enlargement (GBE) or hydrops in the acute phase. Although GBE is highly specific to KD, epidemiological data on GBE have not been updated. In this study we evaluated the occurrence rate of GBE in KD and characterized the clinical features of patients who developed GBE. METHODS: The present study was a prospective, observational study. The maximum longitudinal area of the gallbladder and the common bile duct diameter in KD patients were measured by ultrasonography at the start of initial intravenous immunoglobulin (IVIG) therapy (day 0) and on days 7, 30, and 60 of therapy. The primary outcome was the complication rate of GBE (z- score ≥2.0) on day 0. The secondary outcome was the association of GBE with cholestasis, unresponsiveness to IVIG, and coronary artery lesions (CAL). RESULTS: Gallbladder enlargement occurred in 35% (35/101) of patients on day 0. Cholestasis and severe patients (Kobayashi score [KS] ≥5) were more common in the GBE group (20.6% vs. 1.6%, p = 0.002, and 54.3% vs. 15.2%, p < 0.001, respectively). In patients with a KS of ≤4, the non-responder rate was higher in the GBE group (44% vs. 20%, p = 0.0495) but did not differ in those with a KS of ≥5 (21% vs. 20%, p = 0.95). The rate of CAL occurrence did not differ significantly between the groups (8.6% vs. 6.1%, p = 0.64). CONCLUSIONS: Gallbladder enlargement occurred in 35% of KD patients and was associated with cholestasis. Gallbladder enlargement may not only be a diagnostic finding, but also a severity marker in KD patients.

Follow-Up Duration of Echocardiography in Patients with Kawasaki Disease with No Initial Coronary Aneurysms.

OBJECTIVE: To evaluate the optimal duration of echocardiographic follow-up in patients with Kawasaki disease without an initial coronary aneurysm. STUDY DESIGN: In this single-center, retrospective, observational study, we reviewed the results of follow-up echocardiography in children with Kawasaki disease enrolled in the Prospective Observational Study on Stratified Treatment with Immunoglobulin Plus Steroid Efficacy for Kawasaki Disease from a children's hospital. The main enrollment criterion was the absence of coronary aneurysms, defined as a maximum z-score (Zmax) ≥2.5, in the proximal right coronary artery and the proximal left anterior descending artery within 9 days from treatment initiation. The primary outcome was Zmax on follow-up echocardiography at up to 5 years. RESULTS: Among 386 patients, 106 (27.5%) received prednisolone with intravenous immunoglobulin for first-line therapy, and 57 (14.8%) showed a poor response. Echocardiography at 1 month detected 9 patients with a Zmax ≥2, including 3 (0.8%) with coronary aneurysms requiring additional antithrombotic treatment and observation. Of 7 patients (1.8%) with normal echocardiographic findings at 1 month but a Zmax ≥2 later, 2 were lost to follow-up and 5 experienced spontaneous resolution, but none of the 7 patients required any change in management. CONCLUSIONS: The optimal duration of echocardiographic follow-up may be 1 month in patients with no initial coronary aneurysms and a Zmax <2 at 1 month. Coronary artery abnormalities observed after 1 month are rare and mostly benign in this category of patients.

Relationship Between Body Temperature and Heart Rate in Children With No Other Apparent Cause of Tachycardia.

OBJECTIVE: The aim of the study was to investigate the normal heart rate range for each body temperature in patients visiting the emergency department (ED) with no other, apparent, coexisting factors causing tachycardia. METHODS: This was an observational study conducted in the ED at a single children's hospital between April 1, 2014, and March 31, 2017. Data on all visits were extracted from the electronic triage system and were excluded if they indicated the presence of factors other than body temperature potentially increasing the heart rate. We created age-dependent heart rate percentile curves for body temperature in 6 age categories: 0 to younger than 3 months, 3 to younger than 12 months, 1 to younger than 2 years, 2 to younger than 5 years, 5 to younger than 10 years, and 10 years or older. The curves were created for the body temperatures of 36.0°C to 38.0°C for the 0 to younger than 3 months age group and for body temperatures of 36.0°C to 40.5°C for the other age groups. RESULTS: Of the 113,242 patients included, 61,321 were analyzed. The percentile curves across all age groups were similar despite differences in the baseline heart rate. Heart rate increase was steepest between 37.0°C and 38.0°C at a rate of approximately 20 beats per minute per degree Celsius for all groups. Compared with previous studies in the outpatient setting, including the ED, heart rate was lower in younger patients and was similar among older patients. CONCLUSIONS: We created new, age-dependent heart rate percentile curves for body temperature for use in the ED setting. In outpatients, the effect of coexisting factors affecting heart rate, such as crying, may be higher among younger patients.

Evaluation of a Kawasaki Disease Risk Model for Predicting Coronary Artery Aneurysms in a Japanese Population: An Analysis of Post RAISE.

OBJECTIVES: To test the performance of the Son risk score, which was created to predict coronary artery abnormalities from baseline variables in North American patients with Kawasaki disease. STUDY DESIGN: The dataset from Post RAISE, the largest prospective cohort study of Japanese patients with Kawasaki disease to date, was used for the present study. With high risk defined as ≥3 points, sensitivity, specificity, positive predictive value, and negative predictive value for coronary artery abnormality development were calculated. To evaluate the effect of each risk factor in the Son score, the OR and 95% CIs were calculated using logistic regression analysis with the presence of coronary artery abnormality at 1 month after disease onset. RESULTS: Post RAISE enrolled 2628 consecutive patients with Kawasaki disease, and 304 patients had a high-risk score, of whom 15.1% showed coronary artery abnormality. At the cutoff ≥3 points, the sensitivity was 37.7%, and the specificity was 87.2%. The maximum z score at baseline ≥2.0 (OR 3.5, 95% CI 2.3-5.2) and age <6 months at disease onset (OR 3.2, 95% CI 1.9-5.4), were significantly associated with coronary artery abnormality development. However, a high concentration of C-reactive protein was not associated with coronary artery abnormality. The area under the receiver operating characteristic curve for the Son score was 0.65 (95% CI 0.59-0.71). CONCLUSIONS: The Son score had insufficient sensitivity and good specificity in a Japanese cohort of patients with Kawasaki disease. Among the variables comprising the Son score, a large baseline z score and young age at disease onset were significant, independent predictors of coronary artery abnormality development.

Risk factors of bacteremia in children hospitalized with community-acquired pneumonia: A nested case-control study.

OBJECTIVE: To assess the risk factors of bacteremia in children hospitalized with community-acquired pneumonia (CAP). STUDY DESIGN: The present, nested, case-control study enrolled a cohort of patients with CAP aged < 18 years who were hospitalized at Tokyo Metropolitan Children's Medical Center or Tama-Hokubu Medical Center between March 2010 and February 2018. Among the cohort with blood cultures (BCs), patients with bacteremia were identified and matched with five control patients based on their treatment facility, underlying disease, and age. Conditional logistic regression was used to calculate the odds ratios (ORs) of bacteremia for risk factor candidates. RESULTS: BCs were obtained for 2,383 (84%) of the 2,853 patients in the CAP cohort. Of those with BCs, 34 (1.4%) had bacteremia. S. pneumoniae and H. influenzae accounted for 26 (76%) and four (12%) instances of the bacteremia pathogens, respectively. Bacteremia occurred more frequently among patients hospitalized in the spring than during other seasons (P = 0.022). On multivariate analysis, the severity of pneumonia was not associated with bacteremia incidence (OR: 0.92 [0.30-2.85]) while a white blood cell count > 16,000/µL (OR: 5.90 [2.14-16.3]) was shown to be a significant risk factor. The OR of the need for a ventilator on admission day was significantly high (28.4 [3.02-1374]) on univariate analysis, but the subject pool was too small to determine its significance on multivariate analysis. CONCLUSIONS: The results of the present study supported BC collection in patients with leukocytosis and in those requiring ventilator use on admission.

Incidence and aetiology of serious viral infections in young febrile infants.

AIM: While the incidence and aetiology of serious bacterial infections among febrile infants younger than 90 days old are well studied, those concerning viral infection are not. There are severe life-threatening viral infections requiring immediate intense therapy. The objective of the study is to describe the incidence and aetiology of serious viral infections (SVI) among young febrile infants. METHODS: A retrospective audit was performed covering all the febrile infants younger than 90 days old admitted to a paediatric emergency department in Japan from 2011 to 2013. SVI was defined as a viral illness that may result in permanent organ dysfunctions or life-threatening complications. Diagnostic investigation consisted of urine and blood culture for all infants, cerebrospinal fluid cultures for infants who do not fulfil the low-risk criteria, rapid antigen tests for several viruses in infants with specific symptoms and blood and/or cerebrospinal fluid polymerase chain reaction of possible viruses for infants with fever without a localising source. RESULTS: Of 275 cases, 32 and 45 cases were diagnosed as serious viral and bacterial infections, respectively. Intensive care unit admission occurred for three viral and four bacterial infections. Viral aetiology consisted of respiratory syncytial virus (11 cases), aseptic meningitis (9 cases), enterovirus (6 cases), influenza virus (3 cases), rotavirus (2 cases) and herpes simplex virus-1 (1 case). Respiratory (14 cases), central nervous (12 cases) and circulatory (6 cases) systems were affected. CONCLUSION: SVI was observed in 11.6% of febrile young infants in a paediatric emergency department.

Metered-dose inhaler ipratropium bromide for children with acute asthma exacerbation: A prospective, non-randomized, observational study.

BACKGROUND: Ipratropium bromide (IB), when administered with ß2-agonists, is effective in reducing hospital admissions of children presenting to the emergency department (ED) with severe asthma. While IB is commonly delivered in its nebulized form, using a metered-dose inhaler (MDI), can, reportedly, shorten patients' length of stay in the ED. However, the effectiveness and safety of IB administration using an MDI with a spacer have not been established. This study aimed to investigate the effectiveness and safety of MDI-delivered IB in pediatric patients with acute asthma exacerbation. METHODS: This prospective, non-randomized, observational study included patients aged ≥4 years with a history of severe asthma exacerbation. Patients received IB via MDI with a spacer three times at 20-min intervals. IB use was determined by the physicians' treatment policy. Propensity score matching was used to adjust the confounding factors related to IB administration. RESULTS: Of the 158 patients, 88 were treated with IB and 70 were treated without IB. A propensity score-matching analysis extracted 54 patients from each group. We found no statistical difference in the admission rate of the two groups (IB group: 25.9% vs non-IB group: 31.5%; P = 0.67). The post-treatment modified pulmonary index scores (mean ± SD) were also similar (IB: 6.6 ± 2.0 vs non-IB: 6.3 ± 2.5; P = 0.53). Only one patient (1.0%) treated with IB experienced vomiting, which resolved spontaneously. CONCLUSION: The metered-dose inhaler IB was ineffective in reducing the admission rate possibly because it was less effective than a nebulizer for IB inhalation.

Predicting serious bacterial infection in febrile young infants utilizing body temperature.

BACKGROUND: Febrile young infants have a high risk of serious infection. Although measuring vital sign parameters can serve as a rapid and effective assessment in these patients, their predictive value for serious bacterial infection (SBI) has not been fully investigated. METHODS: This retrospective observational study enrolled febrile (>38.0°C) infants aged <90 days at the time of presentation. Data from the emergency room triage database at Tokyo Metropolitan Children's Medical Center for the period 1 November 2011-30 November 2013, were reviewed. Variables included patient age, gender, and vital sign data, including body temperature, pulse rate, oxygen saturation, definitive diagnosis, and disposition. RESULTS: Two hundred and sixty-nine patients were included, with a mean age of 55 days, and 158 (58.7%) were male. Of the total, 43 patients had an SBI. On logistic regression, body temperature ≥38.5°C (OR, 2.80; 95%CI: 1.37-5.74) was a significant predictor of SBI. CONCLUSION: High-grade fever was found to be a significant predictor of SBI in febrile young infants.

Retrospective observational study indicates that the paediatric assessment triangle may suggest the severity of Kawasaki disease.

AIM: We examined whether the paediatric assessment triangle (PAT) could predict the severity of Kawasaki disease. METHODS: We enroled patients diagnosed with Kawasaki disease between July 2012 and June 2016 at the emergency department of Tokyo Metropolitan Children's Medical Center in Tokyo, Japan. Triage nurses assigned participants to unstable or stable PAT groups. We compared the incidence of coronary artery aneurysms (CAA), the Kobayashi score, which measures resistance to intravenous immunoglobulin treatment, and the incidence of initial treatment resistance. RESULTS: Of the 420 participants, who were aged 0-145 months with a mean age of 31.2 ± 23.9 months, 66 (16%) were assigned to the unstable PAT group. The incidence of CAA was similar between the two groups. The percentage of unstable PAT group participants with a Kobayashi score of at least five points (39 versus 18%, p < 0.001) and initial treatment resistance (25 versus 15%, p = 0.047) were significantly higher than in the stable PAT group. Unstable PAT was an independent risk factor for initial treatment resistance (odds ratio 2.02, 95% confidence interval 1.05-3.90, p = 0.035). CONCLUSION: An unstable PAT was able to predict the severity of Kawasaki disease when measured by a higher rate of initial treatment resistance.

Bradycardia Associated with Prednisolone in Children with Severe Kawasaki Disease.

OBJECTIVE: To identify the prevalence of bradycardia associated with use of prednisolone in patients with Kawasaki disease and analyze the association between bradycardia and responsiveness to intravenous immunoglobulin (IVIG). STUDY DESIGN: We performed a retrospective cohort study of 176 patients with severe Kawasaki disease admitted to the Tokyo Metropolitan Children's Medical Center between March 2010 and December 2015. The group treated with IVIG plus prednisolone therapy from February 2012 was compared with the control group who received IVIG monotherapy before this date. The primary outcome was the prevalence of bradycardia, defined as heart rate less than the first percentile for normal children. Next, we determined whether bradycardia was associated with the clinical course in the patient subgroup treated with IVIG plus prednisolone therapy. RESULTS: The prevalence of bradycardia was significantly higher in the IVIG plus prednisolone subgroup than in the IVIG group (79.1% vs 7.1%; P?

Tachycardia may prognosticate life- or organ-threatening diseases in children with abdominal pain.

BACKGROUND: Abdominal pain is common in children, but expeditious diagnosis of life- or organ-threatening diseases can be challenging. An evidence-based definition of tachycardia in children was established recently, but its diagnostic utility has not yet been studied. OBJECTIVE: To test the hypothesis that abdominal pain with tachycardia may pose a higher likelihood of life- or organ-threatening diseases in children. METHODS: A nested case-control study was conducted in a pediatric emergency department in 2013. Tachycardia was defined as a resting heart rate of more than 3 standard deviations above the average for that age. Life- or organ-threatening diseases were defined as "disorders that might result in permanent morbidity or mortality without appropriate intervention." A triage team recorded vital signs before emergency physicians attended patients. Patients with tachycardia (cases) and without tachycardia (controls) were systematically matched for age, sex, and month of visit. The groups were compared for the presence of life- or organ-threatening diseases. RESULTS: There were 1683 visits for abdominal pain, 1512 of which had vital signs measured at rest. Eighty-three patients experienced tachycardia, while 1429 did not. Fifty-eight cases and 58 controls were matched. Life- or organ-threatening diseases were more common in the case group (19%) than the control group (5%, p=0.043). The relative risk of tachycardia to the presence of the diseases was 3.7 (95% confidence interval 1.2-12.0). CONCLUSION: Tachycardia significantly increased the likelihood of life- or organ-threatening diseases. Tachycardia in children with abdominal pain should alert emergency physicians to the possibility of serious illness.

IPRATROPIUM BROMIDE FOR ACUTE ASTHMA IN CHILDREN: A RETROSPECTIVE TRIAL.

BACKGROUND: Inhaled anticholinergics such as ipratropium bromide (IB), when administered with ß2-agonists, are effective in reducing hospital admissions of children presenting to the emergency department with moderate to severe asthma. However, treatment of acute asthma with IB is still uncommon in Japan. The aim of this study was to investigate the effectiveness and safety of IB for the treatment of pediatric acute asthma. METHODS: We conducted a retrospective study to compare the admission rate of patients who received IB with those who did not. Patients aged 4 years or older with a history of moderate to severe attacks were included. For analysis, propensity score matching was used to adjust the confounding factors related to IB use. Patients received IB by metered-dose inhaler (40µg per dose) with a spacer three times at 20-min intervals. RESULTS: Among 175 patients included in the analysis, 102 patients were treated with IB (IB group) and 73 patients were treated without IB (Non-IB group). A propensity score matching analysis extracted 63 patients from each group. There was no statistical difference between the two groups in terms of admission rate (IB group 12.7% vs Non-IB group 9.5%; p=0.78). One patient (1.0%) treated with IB experienced dryness of the mouth, which resolved spontaneously. CONCLUSIONS: The admission rate did not decline with IB use. Several confounding factors could have influenced and limited our results. A prospective study is needed to investigate the effectiveness of IB in Japan.

Pediatric hypervirulent Klebsiella pneumoniae septic arthritis.

Cases of infection with hypervirulent Klebsiella pneumoniae are gradually increasing in number, and cause life-threatening community-acquired infection even in immunocompetent patients. A 14-year-old boy developed septic hip arthritis due to hypervirulent K. pneumoniae (sequence type 23, serotype K1, magA positive). The patient initially seemed to have been successfully treated with antibiotics and surgical intervention, but septic arthritis developed into osteomyelitis of the femoral head and myositis, which required long-term antibiotic therapy and additional surgical intervention. This is the first pediatric case of hypervirulent K. pneumoniae septic hip arthritis. Treatment plans should mainly consist of antibiotic therapy and surgical intervention. Clinicians, even pediatricians, in developed countries should be aware of the increasing incidence of hypervirulent Klebsiella pneumoniae infection.

Neonatal Staphylococcus lugdunensis urinary tract infection.

Staphylococcus lugdunensis is a known pathogen of infective endocarditis, but not of urinary tract infection. We report a previously healthy neonate without congenital anomalies of the kidney and urinary tract who developed urinary tract infection due to Staphylococcus lugdunensis, illustrating that Staphylococcus lugdunensis can cause urinary tract infection even in those with no urinary tract complications.