松原 大輔

School refusal behavior, defined as a child's prolonged voluntary absence from school for reasons unrelated to illness and/or economic hardship, is a growing concern in Japan. The COVID-19 pandemic has worsened this issue by disrupting children's lives. This review summarizes the prevalence, contributing factors, and health implications of school refusal, particularly in the context of COVID-19. A literature review of government reports and PubMed-indexed studies indicates that school refusal in Japan has been rising for eleven years, reaching a record 340,000 cases in 2023. Middle school students (6.7%) were the most affected, followed by elementary school students (2.1%). The pandemic intensified school-related, family-related, and child-related risk factors. School closures disrupted routines, reduced peer interactions, and increased social isolation, contributing to higher rates of anxiety and depression. Reports of suicides and mental health disorders among children have also surged. Family stressors, including economic hardship and parental mental health struggles, further exacerbate school refusal. Additionally, remote learning has widened socioeconomic disparities in access to education, leaving vulnerable children at greater risk. Addressing school refusal requires a multifaceted approach involving schools, families, healthcare providers, and policymakers. School-based interventions, mental health approach, and flexible educational programs would be essential. The Japanese government's "COCOLO Plan" represents progress toward a more inclusive education system, and a comprehensive, interdisciplinary strategy is needed. Ensuring all children receive the necessary support to reengage with education is critical to overcoming the long-term challenges posed by school refusal.

We report a rare case of pediatric supraclavicular pyogenic lymphadenitis presenting with an "asymmetrical shoulder" in a five-year-old boy. The boy developed right neck and shoulder pain following the resolution of cellulitis at the site of insect bites on his right forearm. Despite the absence of visible inflammation in the shoulder or proximal lymph nodes, short tau inversion recovery magnetic resonance imaging (STIR-MRI) revealed an enlarged supraclavicular lymph node with surrounding edema. He fully recovered following intravenous antibiotic treatment. This case highlights that lymphadenitis in remote drainage sites, such as the supraclavicular nodes, may develop even after the resolution of distal cellulitis at the primary site. Notably, in the present case, inflammation was absent in the anatomically proximal lymph nodes (such as those at the elbow or subclavicular lymph nodes) and appeared only in the supraclavicular region. Lastly, the asymmetrical shoulder appearance may serve as a valuable clinical sign of the underlying lymphadenitis. We also discuss key considerations when encountering supraclavicular lymphadenitis, which carries a high risk of malignancy at all ages.

BACKGROUND: Determining risk factors by echocardiography to prevent major adverse cardiac events (MACE) is crucial in pediatric patients with hypertrophic cardiomyopathy. Recent studies have shown that left atrial (LA) stiffness may serve as surrogate marker in children, to differentiate elevated pulmonary capillary wedge pressure from normal. METHODS: We retrospectively enrolled 239 pediatric patients with hypertrophic cardiomyopathy. They were divided into 2 groups: MACE (n=79) and non-MACE (n=160) groups. Noninvasive LA stiffness was calculated as the ratio of average E/e' to peak LA strain obtained by 2-dimensional speckle-tracking echocardiography. Baseline evaluation was defined as the echocardiogram performed at the time of referral, before the occurrence of a MACE, including appropriate implantable cardioverter-defibrillator intervention, myomectomy, heart transplant, or cardiac death. RESULTS: The MACE group showed significantly decreased left ventricular peak longitudinal strain compared with the non-MACE group, with no significant difference in left ventricular ejection fraction. Peak LA strain was significantly reduced (22.5±7.1% versus 30.4±7.3%; P<0.001), whereas LA stiffness was significantly increased (median 0.57 [IQR, 0.37-0.91]%-1 versus 0.31 [IQR, 0.22-0.42]%-1; P<0.001) in the MACE group. LA stiffness was the superior-most index for predicting MACE (C-index, 0.75; cutoff value, 0.31%-1), and even in cross-validation, the C-index consistently demonstrated the highest predictive ability (LA stiffness, 0.746 [95% CI, 0.737-0.753]). Moreover, LA stiffness was independently associated with increased risk of MACE (HR, 1.12 [95% CI, 1.07-1.17]; P<0.001). CONCLUSIONS: LA stiffness is a newly described index, which may be of incremental value in predicting risk of MACE in pediatric patients with hypertrophic cardiomyopathy.

AIM: To determine whether ChatGPT generates a manuscript with a "human touch" with appropriate inputs, and if yes, what's the difference between human writing versus ChatGPT writing. This is because the presence or absence of human touch may characterize human writing. METHODS: A descriptive study. The first author wrote a Disagreement Letter (Letter 1). Then, disagreement points and "human touch" were provided as input into ChatGPT-4 and tasked with generating a Letter (Letter 2). The authors, seven experienced researchers, and ChatGPT evaluated the readability of Letters 1 and 2. RESULTS: The authors, researchers, and ChatGPT, all reached the same conclusions: the human-written Letter 1 and the ChatGPT-generated Letter 2 had similar readability and similarly involved human touch. Some researchers and ChatGPT recognized slight differences in formal or informal and personal or nonpersonal tones between them, which they considered may not affect paper acceptance. CONCLUSIONS: Human touch is not humans' exclusive possession. The distinction between the human writing versus ChatGPT writing is considered to be present not in the output (manuscript) but in the process of writing, that is, the presence or absence of a joy of writing. Artificial intelligence should aid in enhancing, or at the very least, not impede the human joy. This discussion deserves ongoing exploration.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) presents some clinical overlap with Kawasaki disease (KD). Although KD is common in Japan, the clinical characteristics of MIS-C in Japan remain unknown. Therefore, we aimed to determine the epidemiological and clinical features of MIS-C in Japan. METHODS: Using a case reporting form, a nationwide registry was created between November 2020 and March 2023, involving 2,080 facilities throughout Japan. We prospectively and retrospectively enrolled patients with MIS-C. The primary outcomes were the number and incidence rates of children with MIS-C. The secondary outcomes included clinical features, such as KD phenotype, organ involvement, shock, intensive care unit admission, and coronary artery lesions. RESULTS: Among 398 patients registered, central review identified 129 MIS-C cases (mean age: 8·8 ± 3·7 years). The overall incidence rate was estimated to be 1·5 per 100,000 COVID-19 cases, exhibiting a decline as the COVID-19 pandemic progressed, from 12·3 cases (Pre-Delta) to 1·3 cases (Omicron); 80% of MIS-C cases occurred during the Omicron variant predominant period, and 72% of children with MIS-C met the KD criteria. Cardiovascular (88%) and gastrointestinal (90%) involvement were frequent. In Japan, MIS-C cases showed comparatively less severe clinical features, with shock in 29% and admission to the intensive care unit in 12% of cases. Coronary artery lesions were identified in 15 cases (11·6%), irrespective of the presence of shock. No fatalities were reported. CONCLUSION: The incidence of MIS-C was low in Japan. The clinical features distinctively exhibited a more KD-like phenotype, with less severe clinical features.

AIMS: Principal strain (PS) analysis using 3D speckle-tracking echocardiography enables us to simultaneously measure 3D ventricular volumes and strains. PS quantifies 3D deformation by defining not only amplitude but also direction of principal myocardial contraction (PS angle). This study aims (i) to validate volumetric and functional parameters using PS analysis in volume-overloaded right ventricle (RV) of repaired tetralogy of Fallot (rTOF) vs. cardiac magnetic resonance (CMR) and (ii) to describe PS analysis indices in patients undergoing pulmonary valve replacement (PVR). METHODS AND RESULTS: Sixty-four paediatric patients with rTOF (12.4 ± 5.2 years) and 58 age-matched healthy children (12.8 ± 3.7 years) were prospectively included. We calculated PS magnitude [global PS (GPS)] and angle, indexed RV end-diastolic and end-systolic volumes (EDVi and ESVi), RV ejection fraction (EF), and conventional strains. Among rTOF patients, 32 CMRs were available. First, we validated volumetric parameters obtained by PS analysis against CMR. Second, we compared these indices between rTOF patients and controls. Lastly, we evaluated the discriminative value of PS analysis in PVR. PS analysis and CMR measurements showed good correlations (EDVi, r = 0.80; ESVi, r = 0.74; and EF, r = 0.70, P < 0.001). GPS showed the highest correlation with 3D-EF (r = -0.84, P < 0.001). rTOF patients exhibited nearly doubled RV volume and significantly decreased 3D-EF and conventional strains. PS magnitude also decreased in rTOF patients, with altered PS angles in RV free wall. Volume measurements of RV showed the highest predictive value for discriminating PVR (+) by receiver operating characteristic analysis, followed by PS functional parameters. CONCLUSION: PS analysis is a reliable and reproducible method for both volumetric and functional analysis of volume-overloaded RV in rTOF, which can be of incremental value for defining the indications for PVR.

The most important purpose of medical meetings is to share knowledge with the audience. Medical meetings should be audience-friendly. The presenter and chairperson play crucial roles in these meetings. We wish to put forward some personal proposals to make meetings audience-friendly. For the presenter, state the conclusion or significance first (in the case of case presentation), cite a fundamental article only, and do not skip reading in the summary slide. For the chairperson, be a timekeeper, stop the presentation when there are important mistakes, and choose a question that illustrates the significance of the study and thus interests the audience. All the meeting participants should understand this and support audience-friendly meetings.

Thermal airway injuries, usually accompanied by facial burns, require emergency management. We encountered a pediatric case of a late airway-scalding injury without any initial signs of scalding on the face or inside the oral cavity. A 16-month-old boy was accidentally exposed to boiling water from overhead and developed tachypnea and dyspnea at 8 h after the injury. When he visited our hospital at 12 h after the injury, there were no scalding-related findings on his face or inside his oral cavity; however, severe laryngeal edema was observed, which required emergency intubation. Thermal airway injuries can occur later, even if there is no evidence of facial or oral scalding immediately after the injury. Airway injuries should be considered when a patient has been exposed to hot water from overhead.

A manuscript written not adhering to the fundamentals of academic writing (so-called paper-writing rules) may be rejected before the significance of the study is recognized. Submitting authors, especially those with little experience, may neglect such fundamentals. A simple checklist, which would enable the authors to check whether a manuscript for submission adheres to such fundamentals, should appear at the beginning of the Author Guidelines of medical journal. This checklist may contribute to writing a manuscript following the fundamentals of academic writing, thereby preventing rejection based solely on the writing style.

BACKGROUND: Niemann-Pick disease type C (NPC) is an autosomal recessive inherited and neurodegenerative disorder. Approximately 10% of NPC patients have acute liver failure and sometimes need liver transplantation (LT), and 7% reportedly develop inflammatory bowel disease (IBD). We report the case of a girl with NPC who had a re- accumulation of cholesterol in the transplanted liver and NPC-related IBD. CASE REPORT: The patient underwent living donor liver transplantation (LDLT) due to severe acute liver failure caused by an unknown etiology inherited from her father. At 1 year and 6 months (1Y6M), she developed neurological delay, catalepsy, and vertical supranuclear gaze palsy. The foam cells were found in her skin, and fibroblast Filipin staining was positive; hence, she was diagnosed with NPC. It was identified that her father had NPC heterozygous pathogenic variant. At 2 years, she had anal fissure, skin tag and diarrhea. She was diagnosed with NPC-related IBD, using a gastrointestinal endoscopy. Three years after LT, liver biopsy revealed foam cells and numerous fatty droplets. At 8 years, broken hepatocytes and substantial fibrosis were observed. She died from circulation failure due to hypoalbuminemia at 8Y2M. CONCLUSIONS: In NPC, load of cholesterol metabolism is suggested to persist even after LT. LDLT from NPC heterozygous variant donor was insufficient to metabolize cholesterol overload. In NPC patients, the possibility of cholesterol re-accumulation should be considered when LT is performed. NPC-related IBD should be considered when NPC patients have anorectal lesions or diarrhea.

AIMS: We hypothesized left atrial (LA) stiffness may serve as a surrogate marker in children to differentiate elevated pulmonary capillary wedge pressure (PCWP) from normal and help detect diastolic dysfunction in myocardial injury due to multisystem inflammatory syndrome in children (MIS-C). METHODS AND RESULTS: We validated LA stiffness in 76 patients (median age 10.5 years), 33 had normal PCWP (<12 mmHg) and 43 had elevated PCWP (≥12 mmHg). LA stiffness was applied to 42 MIS-C patients [28 with myocardial injury (+) and 14 without myocardial injury (-)], defined by serum biomarkers. The validation group consisted of a group with and without cardiomyopathies, whose PCWP values ranged from normal to severely elevated. Peak LA strain was measured by speckle-tracking and E/e' from apical four chamber views. Noninvasive LA stiffness was calculated as: LAStiffness=E/e'LAPeakStrain (%-1). Patients with elevated PCWP showed significantly elevated LA stiffness [median 0.71%-1 vs. 0.17%-1, P < 0.001]. Elevated PCWP group showed significantly decreased LA strain (median: 15.0% vs. 38.2%, P < 0.001). Receiver operator characteristic (ROC) curve for LA stiffness yielded an area under the curve (AUC) of 0.88 and cutoff value of 0.27%-1. In MIS-C group, ROC curve yielded an AUC of 0.79 and cutoff value of 0.29%-1 for identifying myocardial injury. CONCLUSION: In children with elevated PCWP, LA stiffness was significantly increased. When applied to children with MIS-C, LA stiffness classified myocardial injury accurately. LA stiffness and strain may serve as noninvasive markers of diastolic function in the pediatric population.

BACKGROUND: Principal strain (PS) analysis quantifies three-dimensional myocardial deformation using three-dimensional speckle-tracking echocardiography. It defines both the amplitude and direction of the principal myocardial contraction, expressed as PS, and a perpendicular secondary strain of lower intensity. The aims of this study were to apply PS analysis to describe the contractile pattern in the single right ventricle (SRV) functioning as a systemic chamber in hypoplastic left heart syndrome, compared with the normal left ventricle (LV) and right ventricle (RV), and to compare SRV function using conventional echocardiographic evaluations. METHODS: Fifty-four post-Fontan patients with hypoplastic left heart syndrome and age-matched control subjects (normal LV, n = 64; normal RV, n = 48) underwent computation of PS lines, ejection fraction (EF), end-diastolic volume indexed to body surface area, PS, secondary strain, circumferential strain, and longitudinal strain. The PS lines were compared between groups. Linear regressions with coefficient determination (R2) of strains, fractional area change, and tricuspid annular plane systolic excursion with EF and end-diastolic volume index were assessed in SRV. Additionally, the hypoplastic left heart syndrome cohort was equally divided into two groups with higher and lower EFs, followed by comparison of all parameters. RESULTS: The pattern of PS lines demonstrated a left-handed direction in the anterior free wall, a right-handed direction in the posterior free wall, and a circumferential direction in the medial wall in SRV. In contrast, in the normal LV, the principal contraction is in the circumferential direction, whereas in the normal RV, it is predominantly longitudinal. The R2 values for PS, secondary strain, and circumferential strain on EF were high (0.88, 0.72, and 0.90, respectively), whereas the R2 value for longitudinal strain was comparable with that for fractional area change (0.56 and 0.55). All parameters were independent of end-diastolic volume index. PS lines in the higher EF group showed a more circumferential orientation than in the lower EF group in SRV. CONCLUSION: PS analysis provides a unique functional map of SRV contraction. This map differs from corresponding maps of the normal LV and RV. This may be helpful in understanding the mechanisms of SRV function, although future longitudinal studies are needed.

Perimyocarditis is a rare and serious cardiac complication following COVID-19 vaccination. Young males are most at risk after the second dose. With the introduction of the booster (third) dose, some reports have focused on the risk of perimyocarditis after a booster dose. However, no currently available report in Japan has comprehensively described this phenomenon. A healthy 14-year-old Japanese male, who had completed a two-dose primary series of the BNT162b2 (Pfizer-BioNTech) vaccine six months prior, developed fever and chest pain within 24 hours after a homologous booster dose. He was transferred to our institute because of worsening chest pain. A multiplex PCR test showed no evidence of active viral infections, including SARS-CoV-2. Electrocardiography revealed ST-segment elevation in almost all leads, suggesting pericarditis. Echocardiography showed normal systolic function. Laboratory data demonstrated C-reactive protein levels of 8.8 mg/dL and elevated cardiac damage markers (troponin T, 1.9 ng/mL; creatine phosphokinase, 1527 U/L; MB isoenzyme, 120 U/L), suggesting myocarditis. He was diagnosed with perimyocarditis associated with the booster dose, which was confirmed by cardiac magnetic resonance imaging four days after initial symptoms. Chest pain improved spontaneously along with a resolution of electrocardiographic findings and laboratory data within several days. He was discharged eight days after admission. Perimyocarditis is less frequent after a booster dose than after primary doses. In this case, the patient with booster-dose-associated perimyocarditis showed favorable clinical course without severe sequelae. The patient's clinical course was consistent with findings on previous large-scale reports on primary-dose-associated perimyocarditis and case series on booster-dose-associated perimyocarditis.

The use of untwisting rate as a novel index of LV diastolic function in clinical practice has been limited due to its tedious and time-consuming analysis. Therefore, we simplify the untwist measurement by only measuring the LV apex's recoil rate and validating and applying peak apical recoil rate (PARR) as an index of diastolic dysfunction (DD) in pediatric subjects during increased and decreased lusitropic states. We recruited 153 healthy subjects (mean age 13.8 ± 2.9 years), of whom 48 performed straight leg raising exercise and an additional 46 patients (mean 8.4 ± 5.6 years) with documented pulmonary capillary wedge pressures (PCWP) (validation cohort). In addition, we studied 16 dilated cardiomyopathy patients (mean age 9.5 ± 6.3 years) (application cohort). PARR and isovolumic relaxation time (IVRT) were compared to PCWP. Both PARR and PARR normalized by heart rate (nPARR) were excellent in detecting patients with PCWP ≥ 12 mmHg and greatly superior to IVRT in this respect (AUC: 0.98, 95% CI [0.96, 1.0] vs. AUC: 0.7 95%CI [0.54,0.86]). In DCM patients, PARR and nPARR were greatly decreased compared to controls (- 38.6 ± 18.6º/s vs - 63.1 ± 16.3º /s, p < 0.001) and (- 0.43 ± 0.20 º/ s/min vs - 0.83 ± 0.28º/s/min, p < 0.0001) but increased with straight leg raising exercise (- 59.4 ± 19.4º/s vs - 97.8 ± 39.0 º/s, p < 0.01) and - 0.85 ± 0.36 vs - 1.4 ± 0.62 º/s/min (p < 0.0001) respectively. PARR and nPARR successfully detected increased and decreased lusitropic states and superior to IVRT in correlation with PCWP. This highly reproducible parameter offers incremental value over traditional indices of DD and may potentially serve as a useful index of elevated PCWP in children.

Ovarian vein thrombosis (OVT) usually occurs on the right side in women with underlying conditions such as pelvic diseases and thrombophilia or during the postpartum period. Here, we present a patient with bilateral OVTs without underlying conditions. A 63-year-old woman without remarkable past or family histories complained of mild lower abdominal pain. Computed tomography revealed bilateral OVTs, with the right-sided thrombus nearly progressing into the inferior vena cava. The presence of symptoms and risk of thrombus extension/pulmonary embolism (PE) led us to administer an oral anticoagulant (rivaroxaban) promptly. Her symptom improved gradually and bilateral OVTs disappeared by 3 months without any evidence of PE. The present case suggests that OVT can occur in a woman without underlying conditions, and the use of an anticoagulant may be a treatment option in such a case.

Background In multisystem inflammatory syndrome in children, there is paucity of longitudinal data on cardiac outcomes. We analyzed cardiac outcomes 3 to 4 months after initial presentation using echocardiography and cardiac magnetic resonance imaging. Methods and Results We included 60 controls and 60 cases of multisystem inflammatory syndrome in children. Conventional echocardiograms and deformation parameters were analyzed at 4 time points: (1) acute phase (n=60), (2) subacute phase (n=50; median, 3 days after initial echocardiography), (3) 1-month follow-up (n=39; median, 22 days), and (4) 3- to 4-month follow-up (n=25; median, 91 days). Fourteen consecutive cardiac magnetic resonance imaging studies were reviewed for myocardial edema or fibrosis during subacute (n=5) and follow-up (n=9) stages. In acute phase, myocardial injury was defined as troponin-I level ≥0.09 ng/mL (>3 times normal) or brain-type natriuretic peptide >800 pg/mL. All deformation parameters, including left ventricular global longitudinal strain, peak left atrial strain, longitudinal early diastolic strain rate, and right ventricular free wall strain, recovered quickly within the first week, followed by continued improvement and complete normalization by 3 months. Median time to normalization of both global longitudinal strain and left atrial strain was 6 days (95% CI, 3-9 days). Myocardial injury at presentation (70% of multisystem inflammatory syndrome in children cases) did not affect short-term outcomes. Four patients (7%) had small coronary aneurysms at presentation, all of which resolved. Only 1 of 9 patients had residual edema but no fibrosis by cardiac magnetic resonance imaging. Conclusions Our short-term study suggests that functional recovery and coronary outcomes are good in multisystem inflammatory syndrome in children. Use of sensitive deformation parameters provides further reassurance that there is no persistent subclinical dysfunction after 3 months.

Multisystem inflammatory syndrome in children (MIS-C) is a newly defined hyperinflammatory disease linked to antecedent coronavirus disease 2019. Patients with MIS-C present with various symptoms, and ocular findings such as mild bilateral conjunctivitis are relatively common. However, detailed descriptions of severe ocular reports associated with MIS-C are scarce in the current literature. Here we report a case of MIS-C in a Japanese boy, with severe eye manifestations in the form of anterior scleritis as the primary MIS-C symptom. Detailed ocular examinations by ophthalmologists may be key for clarifying the pathophysiology of MIS-C.

BACKGROUND: The efficacy and safety of continuous intravenous infusion of cyclosporine A (CICsA) in patients with intravenous immunoglobulin-resistant Kawasaki disease are unclear. METHODS: Between 2010 and 2020, 83 patients with Kawasaki disease that was not responsive to intravenous immunoglobulin (total dose ≥ 4 g/kg) were enrolled. All patients were started on CICsA (3 mg/kg/day) and switched to oral cyclosporine A (CsA) (4-6 mg/kg/day). Treatment efficacy, occurrence of coronary artery lesions (CALs), and laboratory parameters were evaluated. Patients were divided into two groups according to CICsA response: the responder group (afebrile ≤24 h after CICsA without additional treatment) and the weak responder group (afebrile >24 h after CICsA requiring additional treatment). RESULTS: Fifty-five patients became afebrile within 24 and 74 h became afebrile in less than 72 h. Adverse events included hypertension in four and hyperkalemia in two patients. Thirty-nine patients were defined as responders and 44 patients as weak responders. There were no significant differences in CAL between the two groups. In weak responders, white blood cells, neutrophils, and C-reactive protein levels were higher, and albumin, immunoglobulin G, and CsA concentration were lower than in responders, indicating that weak responders had more severe inflammatory findings. However, there were no significant differences in CAL. Logistic regression analysis revealed that the response to treatment for CICsA was associated with immunoglobulin G levels at baseline and CsA concentrations the day after CICsA. CONCLUSION: Although CICsA required additional treatments in about half of the cases, a favorable clinical course was observed by using this strategy, especially for reducing CAL.

Background Cardiac dysfunction is a prominent feature of multisystem inflammatory syndrome in children (MIS-C), yet the etiology is poorly understood. We determined whether dysfunction is global or regional, and whether it is associated with the cytokine milieu, microangiopathy, or severity of shock. Methods and Results We analyzed echocardiographic parameters of myocardial deformation and compared global and segmental left ventricular strain between 43 cases with MIS-C ≤18 years old and 40 controls. Primary outcomes included left ventricular global longitudinal strain, right ventricular free wall strain), and left atrial strain. We evaluated relationships between strain and profiles of 10 proinflammatory cytokines, microangiopathic features (soluble C5b9), and vasoactive-inotropic requirements. Compared with controls, cases with MIS-C had significant impairments in all parameters of systolic and diastolic function. 65% of cases with MIS-C had abnormal left ventricular function (|global longitudinal strain|<17%), although elevations of cytokines were modest. All left ventricular segments were involved, without apical or basal dominance to suggest acute stress cardiomyopathy. Worse global longitudinal strain correlated with higher ratios of interleukin-6 (ρ -0.43) and interleukin-8 (ρ -0.43) to total hypercytokinemia, but not absolute levels of interleukin-6 or interleukin-8, or total hypercytokinemia. Similarly, worse right ventricular free wall strain correlated with higher relative interleukin-8 expression (ρ -0.59). There were no significant associations between function and microangiopathy or vasoactive-inotropic requirements. Conclusions Myocardial function is globally decreased in MIS-C and not explained by acute stress cardiomyopathy. Cardiac dysfunction may be driven by the relative skew of the immune response toward interleukin-6 and interleukin-8 pathways, more so than degree of hyperinflammation, refining the current paradigm of myocardial involvement in MIS-C.

BACKGROUND: High-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2 g/kg of IVIG is administered over 10-24 h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds. METHODS: This was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12 h (12H group, double speed), and one that received IVIG over 24 h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration. RESULTS: A total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21 h vs. 21.5 h, p = 0.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037 ± 648 mg/dl vs. 2414 ± 248 mg/dl, p < 0.01). CONCLUSION: The efficacy and safety of IVIG administered over 12 h (double speed) were similar to those administered over 24 h (reference speed). TRIAL REGISTRATION: University Hospital Medical Information Network ( UMIN000014665 ). Registered 27 July 2014 - Prospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000017058.

OBJECTIVE: To investigate whether redness and crusting at the bacille Calmette-Guérin inoculation site (BCGitis), identified during acute illness owing to Kawasaki disease (KD), is an independent risk factor for development of cardiac complications. DESIGN: Retrospective cohort study using data from the nationwide KD survey in Japan. SETTING: Survey respondents included hospitals specialising in paediatrics and hospitals with ≥100 beds and a paediatric department throughout Japan. PATIENTS: We included 17 181 patients with KD across Japan during 2005-2006. MAIN OUTCOME MEASURES: BCGitis and cardiac complications resulting from KD. RESULTS: BCGitis was identified in 7549 (44%) patients with KD. Compared with patients without BCGitis, those with BCGitis were younger, more likely to be male, less likely to have recurrent status and visited a hospital and underwent initial intravenous immunoglobulin (IVIG) treatment earlier after KD onset. In the unadjusted model, patients with BCGitis were significantly less likely to have cardiac complications (crude OR 0.81, 95% CI 0.71 to 0.92). However, after including treatment factors (days of illness at initial IVIG and treatment responsiveness) in the adjusted model, the association was no longer significant (adjusted OR 0.89, 95% CI 0.77 to 1.03), indicating that BCGitis was not an independent factor associated with cardiac complication and might be confounded by treatment factors. CONCLUSIONS: BCGitis was identified in comparatively early illness stages of KD. Our findings indicated that BCGitis was not an independent factor associated with developing cardiac complications but was confounded by prompt initial IVIG administration, which might result in successful treatment and prevention of cardiac complications.

Background Detection of coronary artery lesions (CALs) at initial echocardiography can aid in diagnosing Kawasaki disease (KD) and inform primary adjunctive treatments. We aimed to characterize patients with KD with CALs detected at initial echocardiography. Methods and Results We analyzed data from the nationwide Japanese KD survey that contained information on 103 222 population-based patients diagnosed with KD across Japan during 2011 to 2018. Patients with CALs detected at initial echocardiography were assessed by age, day of illness, and number of principal KD signs (≥3). Multivariable logistic regression analysis was performed to evaluate factors independently associated with CAL detection. Overall, 3707 (3.6%) patients had CALs detected at initial echocardiography. Patients aged <12 and ≥60 months were associated with CAL detection (adjusted odds ratio [95% CI], 1.28 [1.18‒1.39] and 1.32 [1.20‒1.45], respectively; reference, 12‒59 months). Patients with delayed hospital visits were increasingly at higher risk for CAL detection (days 7‒8, 1.84 [1.63‒2.08]; days 9-10, 4.30 [3.58-5.15]; and days ≥11, 9.12 [7.63‒10.90]; reference, days 1-4). Patients with 3 or 4 principal KD signs were independently associated with CAL detection (1.75 [1.63‒1.88]). These patients were significantly more likely to be aged <12 months but were not associated with delayed hospital visit. Younger patients visited at earlier days of illness. Conclusions Timely diagnosis could be beneficial for patients with KD. However, even when the hospital visit occurred early in the course of illness, patients with 3 or 4 principal KD signs, especially younger patients, were at higher risk of CAL detection at initial echocardiography.

BACKGROUND: Imaging of novel coronavirus disease 2019 (COVID-19) has been described in adults, but children have milder forms of disease. Pediatric imaging descriptions are of asymptomatic children, raising the question of whether imaging is needed in this patient group. OBJECTIVE: To describe the utilization and imaging findings in children with COVID-19 along with the comorbidities, treatment and short-term outcomes. MATERIALS AND METHODS: We retrospectively reviewed pediatric patients who had a confirmed positive test for COVID-19 during a 2-month period. We noted symptoms and presence of imaging at presentation. Comorbidities were recorded for children with imaging. Children were categorized as having multisystem inflammatory syndrome in children (MIS-C) if they met criteria for the disorder. For children who were admitted to the hospital, we documented length of hospital stay, need for intensive care unit care/ventilator support, and treatment regimen. We evaluated all imaging for acute/chronic abnormalities including chest radiographs for interstitial or alveolar opacities, distribution/symmetry of disease, zonal predominance, and pleural abnormalities. We performed descriptive statistics and compared children with MIS-C with the cohort using a Fisher exact test. RESULTS: During the study period, 5,969 children were tested for COVID-19, with 313 (5%) testing positive. Of these, 92/313 (29%) were asymptomatic and 55/313 (18%) had imaging and were admitted to the hospital for treatment. Forty-one of 55 patients (75%) with imaging had comorbidities. Chest radiographs were the most common examination (51/55 patients, or 93%) with most demonstrating no abnormality (34/51, or 67%). Children with MIS-C were more likely to have interstitial opacities and pleural effusions. US, CT or MRI was performed in 23/55 (42%) children, 9 of whom had MIS-C. Only one chest CT was performed. CONCLUSION: In our study, most pediatric patients with COVID-19 did not require hospital admission or imaging. Most children with imaging had comorbidities but children with MIS-C were more likely to have no comorbidities. Children with imaging mostly had normal chest radiography. Advanced imaging (US, CT, MRI) was less common for the care of these children, particularly CT examination of the chest and for children without MIS-C.