Abstract Objectives: The early administration of immunoglobulin in Kawasaki disease occasionally results in treatment failure. However, whether this is because severe cases are diagnosed and treated early or due to other factors remains unclear. In this study, we examined the timing of initial immunoglobulin administration and immunoglobulin resistance in cases classified by severity of illness. Methods: This study was a single-hospital, retrospective cohort study of 608 patients who received immunoglobulin within 4 (Early-treatment group, n=225) or between 5 and 7 days (Late-treatment group, n=383) following treatment onset. Cases were classified into four groups: high (n=55), moderate (n=96), low (n=197), and very-low (n=260) risk, based on the Kobayashi score, modified to exclude the day of illness factor. Within each risk group, immunoglobulin resistance was compared between the early- and late-treatment groups. Results: The early-treatment group showed greater immunoglobulin-resistance than the late-treatment group. After severity classification, the cases of high and moderate-risk in the early-treatment group were more immunoglobulin-resistant than in late-treatment group, with odds ratios (95% CI) of 6.7 (1.6-28) and 3.7 (1.6-8.5), respectively. There was no difference in the low and very-low-risk groups. Conclusion: Earlier illness day was a risk factor of immunoglobulin resistance in severe cases.
Abstract Background Persistent low‐grade fever has been observed in some patients during intravenous immunoglobulin (IVIG) therapy for Kawasaki disease (KD); however, smoldering fever (SF) has not previously been reported in patients with KD. This study aimed to clarify the clinical characteristics of SF in patients with KD. Methods A single‐center retrospective cohort study, which included a total of 621 patients who received IVIG therapy, was conducted. Patients with a fever of 37.5–38°C lasting ≥3 days after 2 days of the initial‐IVIG were defined as the SF group. Patients were divided into four groups according to the fever course: SF ( n = 14), biphasic fever (BF, n = 78), non‐fever after initial‐IVIG (NF, n = 384), and persistent fever (PF, n = 145). The clinical features of SF were described and compared between the groups. Results The median duration of fever in the SF group was 16 days, which was longer than that in any other group. The neutrophil fraction after IVIG therapy in the SF group was higher than that in the BF and NF groups but similar to that in the PF group. Repeated IVIG administration in the SF group resulted in increased IgG levels but decreased serum albumin levels. In the SF group, 29% of the patients had coronary artery lesions at 4 weeks. Conclusions The frequency of SF in KD was 2.3%. Patients with SF continued to have moderate inflammatory responses. Repeated administration of IVIG doses was not effective in treating SF, and acute coronary artery lesions were occasionally observed. Active therapeutic intervention was needed.
Abstract Tolvaptan is an oral vasopressin type 2 receptor antagonist that can be used for heart failure patients with hyponatremia or symptomatic congestion. Although the effects of tolvaptan in adults have been well documented, only limited information is available in children. The case of a neonate with congestive heart failure complicated with chylothorax after palliative surgery for transposition of the great arteries treated with tolvaptan is reported. Slow up‐titration to 0.1 mg/kg successfully increased urine output and improved refractory congestive heart failure without hypernatremia. Subsequently, bodyweight and chylothorax decreased gradually. Moreover, the use of tolvaptan reduced the dosage of furosemide. Tolvaptan could be an alternative drug for neonates with congestive heart failure. Further large studies are needed to confirm the efficacy and identify the appropriate dose of tolvaptan in neonates.
Abstract Background The purpose of this study was to predict which patients would require plasma exchange therapy (PEX) using laboratory findings during intravenous immunoglobulin (IVIG) therapy in Kawasaki disease. Methods A retrospective, single‐center, cohort study was conducted. Of the 621 IVIG‐treated patients, 166 patients who received a second IVIG dose on the second day after initiation of IVIG were included. The endpoint was PEX. Participants were divided into two groups: 10 patients who received PEX and 156 patients who did not. The variables were C‐reactive protein (CRP), white blood cell count (WBC), and neutrophil fraction (NEUT) at three time points: pre‐initial IVIG, pre‐second IVIG, and post‐second IVIG. The change ratio (post‐IVIG value/pre‐IVIG value) of each variable, with each IVIG dose, was calculated. Receiver operating characteristic analysis determined the area under the curve (AUC) and cut‐off values. Results The variables with an AUC > 0.9 were CRP (post‐second IVIG), change ratio of CRP (CRP value post‐second IVIG/CRP value pre‐second IVIG), NEUT (pre‐second IVIG), and NEUT (post‐second IVIG). Among these, the variables with high sensitivity were CRP (post‐second IVIG) and the change ratio of CRP (second IVIG), with cut‐off values of 9.52 mg/dL and 0.99, respectively. The sensitivity and specificity of these variables were 100% and 91%, and 100% and 80%, respectively. The combined sensitivity and specificity (95% confidence intervals) of these two variables were 100% (59–100) and 94% (89–97). Conclusion High CRP levels and the change ratio of CRP after the second IVIG dose were associated with PEX.
Percutaneous occlusion of atrial septal defect (ASD) has recently become a standard therapeutic strategy, but little is known about left atrial (LA) function thereafter. The present study aimed to determine LA function in 43 children with ASD and 13 controls based on LA strain measured by two-dimensional echocardiographic speckle tracking (2DE-ST). Among these children, 12 underwent surgery (ASD-S), 31 had device closure (ASD-D), and 13 were included as controls. LA strain was significantly decreased after ASD-D but was not significantly altered after ASD-S, indicating that percutaneous occlusion of an ASD might decrease LA function. Furthermore, the size of the ASD device negatively correlated with LA strain. These results imply that ASD occlusion devices negatively influence LA function and might be important when decided therapeutic strategies for ASD. LA strain measured by 2DE-ST should become a good indicator of LA function after ASD treatment in children.
Abstract Background Long QT syndrome type 8 (LQT8) caused by mutations in CACNA1C has been classified as a very rare and severe type of long QT syndrome accompanied with Timothy syndrome (TS) with extra-cardiac phenotype. Recently, various mutations in CACNA1C have been identified in non-TS patients. However, mutation specific severity in LQT8 has not been elucidated yet, especially for non-TS patients. Purpose We aimed to clarify the clinical characteristics of LQT8 patients. Methods The study consists of 26 LQT8 patients (21 probands and 5 family members). We evaluated their phenotype. Results Table summarizes the clinical characteristics of LQT8 patients. TS patients diagnosed in younger age than those of non-TS. Four TS and one non-TS patients were diagnosed at the age of 0, though the non-TS patient was a son of a patient and asymptomatic. Nine patients suffered symptoms including 7 with cardiac arrest. We identified three TS mutations; classical p.G406R in two and p.G402S in two, and a new TS mutation, p.412M in one. Four of TS patients were symptomatic and two died suddenly at the age of 4 and 5. In contrast, no one died in non-TS patients. Five non-TS patients suffered symptoms in the age of 4,9,15,54 and 64, and the mutations were p.S643F, p.R858H (2 patients), p.K1518E and p.K1591T. Characteristics of TS and non-TS patient TS Non-TS P N (male) 5 (2) 21 (9) Age (range) 0 (0–7) 12 (0–64) 0.004 Symptom Syncope 4 5 0.034 CPA 3 4 0.101 ECG characteristics QT interval 603±40 507±14 0.011 T wave alternans 5 2 <0.001 AV Block 4 1 0.002 Therapy (4 unknown) Beta-blocker 4 7 0.311 Mexiletine 3 1 0.024 ICD implantation 2 2 0.21 Conclusions Although TS patients showed severe phenotype, most of the non-TS patients were asymptomatic. The phenotype in LQT8 are diversely different depend on the mutations, especially between patients with TS and non-TS.
