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.

Neck Hair-Thread Tourniquet Syndrome by Co-sleeping With Family: A Case Report and Literature Review.

Neck hair-thread tourniquet syndrome (NHTTS) is a rare condition that can be a pediatric emergency, occurring when a hair or thread becomes tightly wrapped around a body part, leading to vascular or tissue damage. NHTTS commonly affects infants and young children and can result in severe complications if not promptly diagnosed and treated. The unusual nature of this event, the diffuse petechial hemorrhage on the face, and the presentation of ligature marks extending around the neck led us to admit the child to the general pediatric ward for follow-up and further investigation of the possibility of non-accidental trauma. Co-sleeping is a common cultural practice in Japan where parents sleep in close proximity to their infants. This case report aims to raise awareness among pediatricians and parents about the possibility of NHTTS occurring in infants who co-sleep, particularly when a strand of hair becomes entangled around their neck, about the early detection and appropriate management of NHTTS. And we also summarize the reported NHTTS cases.

A prospective cohort study of sensorineural hearing loss associated with Kawasaki disease.

AIM: About 60 cases of sensorineural hearing loss (HL) have been reported in patients with Kawasaki disease (KD), but the current estimate of its prevalence is uncertain. The present study aimed to determine the prevalence and risk factors of sensorineural HL associated with KD. METHODS: The present, prospective cohort study, conducted from May 2019 to May 2020, evaluated patients with a diagnosis of KD who received the initial therapy and underwent two auditory brainstem response (ABR) tests. HL was defined as a threshold of 40 dB or more, and borderline hearing was defined as a threshold of 30 dB. RESULTS: In total, 107 patients were enrolled, and 75 underwent two ABR tests. Thirty-one patients (30.0%) received prednisolone with their initial intravenous immune globulin and acetylsalicylic acid therapy. HL was present in only one patient who had congenital conductive HL. Five patients had borderline hearing but had normal hearing behavior. There was no significant difference between the patients with normal hearing and those with borderline hearing in terms of the clinical variables. CONCLUSIONS: In Japan, the prevalence of sensorineural HL after KD is not high. It may therefore be unnecessary to perform routine hearing tests for all patients with KD. NAME OF TRIAL REGISTER: Association between Kawasaki Disease and Sensorineural Hearing Loss. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000037019 (the date of registration: June 11, 2019).

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.

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.

Predictor of Early Administration of Antibiotics and a Volume Resuscitation for Young Infants with Septic Shock.

(1) Background: It is critical to administer antibiotics and fluid bolus within 1 h of recognizing sepsis in pediatric patients. This study aimed to identify the predictor of the successful completion of a 1-h sepsis bundle for infants with suspected sepsis. (2) Methods: This is an observational study using a prospective registry including febrile young infants (aged < 90 days) who visited a pediatric emergency department with a core body temperature of 38.0 °C or higher and 36.0 °C or lower. Univariate and logistic regression analyses were conducted to determine the predictor (s) of successful sepsis bundle completion. (3) Results: Of the 323 registered patients, 118 patients with suspected sepsis were analyzed, and 38 patients (32.2%) received a bundle-compliant treatment. Among potential variables, such as age, sex, and vital sign parameters, the logistic regression analysis showed that heart rate (odds ratio: OR 1.02; 95% confidence interval: 1.00-1.04) is a significant predictor of the completion of a 1-h sepsis bundle. (4) Conclusions: We found that tachycardia facilitated the sepsis recognition and promoted the successful completion of a 1-h sepsis bundle for young infants with suspected septic shock and a possible indicator for improving the quality of the team-based sepsis management.

Limited Utility of SIRS Criteria for Identifying Serious Infections in Febrile Young Infants.

(1) Background: Young infants have a high risk of serious infection. The Systematic Inflammatory Response Syndrome (SIRS) criteria can be useful to identify both serious bacterial and viral infections. The aims of this study were to evaluate the diagnostic performance of the SIRS criteria for identifying serious infections in febrile young infants and to identify potential clinical predictors of such infections. (2) Methods: We conducted this prospective cohort study including febrile young infants (aged < 90 days) seen at the emergency department with a body temperature of 38.0 °C or higher. We calculated the diagnostic performance parameters and conducted the logistic regression analysis to identify the predictors of serious infection. (3) Results: Of 311 enrolled patients, 36.7% (n = 114) met the SIRS criteria and 28.6% (n = 89) had a serious infection. The sensitivity, specificity, positive predictive value, and positive likelihood ratio of the SIRS criteria for serious infection was 45.9%, 69.4%, 43.5%, 71.4%, 1.5, and 0.8, respectively. Logistic regression showed that male gender, body temperature ≥ 38.5 °C, heart rate ≥ 178 bpm, and age ≤ 50 days were significant predictors. (4) Conclusions: The performance of the SIRS criteria for predicting serious infections among febrile young infants was poor.

Live attenuated vaccine efficacy six months after intravenous immunoglobulin therapy for Kawasaki disease.

BACKGROUND: Due to the presence of maternal passive antibodies, the measles vaccine is ineffective if administered before age 12-15 months. The optimal timing for administering a live attenuated vaccine (LAV) after intravenous immunoglobulin therapy (IVIG) for Kawasaki disease (KD) has not been fully investigated. The recommended interval between vaccination and IVIG therapy for KD differs by country. The present study aimed to evaluate efficacy of LAV six months after IVIG therapy for KD in Japan. METHODS: The present, single-arm, prospective, interventional study included patients aged 6 months or older with no medical history of measles, rubella, varicella or mumps or vaccinations against these diseases. The subjects received these vaccinations for the first time at six months after IVIG therapy. Virus-specific IgG levels for each virus measured by EIA was examined at nine months after IVIG therapy. If the results were negative, the subjects received a booster vaccination at 12 months after IVIG therapy. The primary outcome was the prevalence of positivity for antibodies after the initial and booster vaccinations. RESULTS: The present study enrolled 32 subjects, 31% of whom were female, with an average age of 10.8 (standard deviation 2.8) months at IVIG therapy. At six months after IVIG therapy, 9% and 6% of the subjects were seropositive for measles and varicella titers, respectively, but were seronegative for the mumps and rubella titers. The seroconversion rate for measles, mumps, rubella, and varicella after the initial vaccination was 88%, 6%, 78%, and 16%, respectively. The seroconversion rate after a booster vaccination was 100% for measles and rubella, 97% for mumps, and 77% for varicella. CONCLUSIONS: The seroconversion rate was low for LAV at six months after a single dose of IVIG for KD, but seroconversion was achievable with a booster vaccination at 12 months. CLINICAL TRIAL REGISTRATION: UMIN-CTR, UMIN000007174, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000008452.

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.

Risk Factors of Coronary Artery Abnormalities and Resistance to Intravenous Immunoglobulin Plus Corticosteroid Therapy in Severe Kawasaki Disease: An Analysis of Post RAISE.

BACKGROUND: Coronary artery abnormalities (CAAs) still occur in patients with Kawasaki disease receiving intensified treatment with corticosteroids. We aimed to determine the risk factors of CAA development and resistance to intensified treatment in Post RAISE (Prospective Observational Study on Stratified Treatment With Immunoglobulin Plus Steroid Efficacy for Kawasaki Disease)-the largest prospective cohort of Kawasaki disease patients to date. METHODS: In Post RAISE, 2648 consecutive patients with Kawasaki disease were enrolled. The present study analyzed 724 patients predicted to be intravenous immunoglobulin (IVIG) nonresponders (Kobayashi score ≥5) who received intensified treatment consisting of IVIG plus prednisolone. The association between the baseline characteristics and CAA at 1 month after disease onset was examined. The association between the baseline characteristics and treatment resistance was also investigated. RESULTS: Maximum Z score at baseline ≥2.5 (odds ratio, 3.4 [95% CI, 1.5-7.8]), age at fever onset <1 year (odds ratio, 3.4 [95% CI, 1.6-7.4]), and nonresponsiveness to IVIG plus prednisolone treatment (odds ratio, 6.8 [95% CI, 3.3-14.0]) were independent predictors of CAA development. Nonresponsiveness to IVIG plus prednisolone was significantly associated with 8 baseline variables. Baseline total bilirubin (odds ratio, 1.4 [95% CI, 1.2-1.7]) was the only significant independent predictor other than the variables included in the Kobayashi score, enabling treatment resistance to be identified at diagnosis. The area under the ROC curve was 0.74 (95% CI, 0.69-0.79). At a cutoff point of 1.0, the sensitivity and specificity for predicting treatment resistance were 71% and 65%, respectively. CONCLUSIONS: In Post RAISE, younger age at fever onset, a larger maximum Z score at baseline, and nonresponsiveness to IVIG plus prednisolone were risk factors significantly associated with CAA development. Nonresponders were able to be identified at diagnosis based on the total bilirubin value. To prevent CAA, more intensified or adjunctive therapies using other agents, such as pulsed methylprednisolone, ciclosporin, infliximab, and Anakinra, should be considered for patients with these risk factors. Registration: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000007133.

Intraoperative Anatomical Findings in Pediatric Clear Cell Meningioma of the Lumbar Spine: Case Report and Literature Review.

Clear cell meningioma (CCM) is a WHO classification Grade II meningioma. It is a very rare disease, of which only 41 cases of spinal cord CCM in children have been reported to date. CCMs sometimes do not have the "dural attachment" that is usually found in meningiomas, and our understanding of the origin of CCMs is therefore controversial. We hereby present a case of pediatric CCM of the lumbar spine, in which we examined intraoperatively, the detailed anatomical location of the tumor. The case is a 10-year-old boy, who presented to our hospital with a 2-month history of lower back and bilateral lower extremity pain upon waking, which gradually worsened. Lumbar spine CT and MRI revealed an intradural extramedullary tumor at the L3 vertebral level, and surgery was performed to remove it. The tumor was in close contact with the dura mater, and also in contact with the cauda equina via the arachnoid. The tumor was likely located primarily between the dura mater and arachnoid. The pathological diagnosis was CCM, with an MIB-1 index of less than 1%. His back pain and bilateral lower extremity pain improved after surgery, and he was discharged from our hospital. Postoperative radiation therapy was not performed. Based on this case, we suggest that intraoperative examination of the anatomical location of these tumors and accumulation of relevant experience are important to elucidate the embryological mechanisms of this rare disease.

Decreased hemoglobin after initial treatment is associated with treatment resistance in Kawasaki disease in Kobayashi risk stratification.

BACKGROUND: Although Kawasaki disease (KD) is known to cause anemia, the relationship between its prognosis and hemoglobin level is less well known. METHODS: We herein performed a secondary analysis of data from a previous study (Post-RAISE). Children aged 6 months to 2 years at the time of KD diagnosis were enrolled. Decreased hemoglobin was defined as a decrease > 10% on post-treatment day 2 compared with the level prior to the initial therapy. RESULTS: Of 1253 KD cases, treatment resistance was observed in 209 (17%) and was significantly more frequent in the decreased hemoglobin group (37/167 vs. 172/1086, P = 0.041). Multivariable logistic regression analysis revealed that decreased hemoglobin was associated with resistance to the initial treatment (odds ratio 1.53; 95% confidence interval 1.00-2.33; P = 0.048). CONCLUSIONS: Decreased hemoglobin was significantly associated with resistance to initial treatment in patients with KD.

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.

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.