Methylprednisolone pulse and prednisolone for intensification of primary treatment in Kawasaki disease patients at high risk of treatment resistance: a multicenter prospective cohort study.

The purpose of this study is to determine whether adding intravenous methylprednisolone pulse (IVMP) to primary adjunctive prednisolone with intravenous immunoglobulin (IVIG) improves treatment resistance and coronary artery aneurysms (CAA) in patients with Kawasaki disease (KD) with a high risk of treatment resistance. This multicenter, prospective, observational study was conducted at 28 hospitals in Japan from October 2016 to June 2020. For patients predicted to be resistant to treatment based on a Kobayashi score ≥ 5 and total bilirubin ≥ 1.0 mg/dL, each hospital independently decided to add IVMP followed by prednisolone, prednisolone alone, or nothing to the primary IVIG therapy. In total, 2856 consecutive KD patients were enrolled; of these, 399 (14.0%) were predicted to be treatment resistant. Patients who were resistant to the primary treatment and required additional treatment comprised 59%, 20%, and 26% of the IVIG-alone group, IVIG-plus-prednisolone group, and IVIG-plus-IVMP group, respectively (P < .0001). The CAA incidence (Z score ≥ 2.5) at month 1 was similar among the treatment groups (6.7%, 4.8%, and 7.3%, respectively; P = .66). CAA occurred more frequently in patients who needed third- or later-line therapy.Conclusions: Primary adjunctive corticosteroid therapy improved the treatment response and suppressed inflammation. However, the study found no benefit of adding IVMP to prednisolone therapy. Patients receiving IVIG alone achieved coronary outcomes comparable to those of patients receiving primary adjunctive corticosteroid therapy although they were more likely to require additional rescue treatment. KD inflammation should be resolved no later than the third line of additional treatment to reduce the risk of CAA.Trial registration: University Hospital Medical Information Network Clinical Trials Registry in Japan ( https://www.umin.ac.jp/ctr/index.htm ) under code UMIN000024937.

Association of Yersinia Infection With Kawasaki Disease: A Prospective Multicenter Cohort Study.

BACKGROUND: Yersinia infection is known to present with Kawasaki disease (KD)-like symptoms although differentiating the 2 has been a challenge. The present study aimed to describe the clinical characteristics and prevalence of Yersinia infection presenting with KD-like symptoms. METHODS: The present, prospective, multicenter study enrolled patients who received a diagnosis of KD between January 2021 and January 2022 at 2 hospitals in Tokyo. Stool samples were collected within 3 days of the start of KD treatment, and cultures were performed for Yersinia . Clinical history and symptoms suggestive of Yersinia infection were also evaluated. RESULTS: During the study period, 141 KD patients were screened and 117 patients with evaluable stool samples were registered. Only 1 patient was positive for Yersinia pseudotuberculosis , which was detected from both stool and blood cultures. The patient was refractory to KD treatment but improved after initiation of appropriate antibiotic therapy. CONCLUSIONS: Routine screening for Yersinia is not appropriate for patients with KD and should be limited to certain patients in high-risk areas and those who are refractory to the standard KD treatment.

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.

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.

Cardiofaciocutaneous syndrome with KRAS gene mutation presenting as chylopericardium.

A 12-year-old female patient with cardiofaciocutaneous syndrome in the presence of a KRAS gene mutation had episodes of pericardial effusion on ultrasound, later confirmed to be chylopericardium, which resolved after a lymphangiography. We discussed herein the pathophysiological background of this rare case and the efficacy of lymphangiography in the treatment of chylopericardium.

Molecular studies reveal MLL-MLLT10/AF10 and ARID5B-MLL gene fusions displaced in a case of infantile acute lymphoblastic leukemia with complex karyotype.

The present report describes a unique infantile acute lymphoblastic leukemia (ALL) case with cryptic mixed-lineage leukemia (MLL) rearrangements with 11q23 chromosomal translocation. MLL break-apart signals were identified by fluorescence in situ hybridization, and transcriptome sequencing revealed MLL-myeloid/lymphoid or mixed-lineage leukemia; translocated To, 10 (MLLT10)/AF10 fusion transcripts. Analysis also revealed a previously unreported MLLT10/AF10-homeobox protein Mohawk (MKX) transcript, where the 5' portion of MLLT10/AF10 at 10p12.31 was fused out-of-frame with the 3' portion of MKX at 10p12.1, which is closely located to MLLT10/AF10. Furthermore, the reciprocal 3'-MLL gene segment was fused in-frame to AT-rich interaction domain (ARID)5B at 10q21. Previously, common allelic variants in ARID5B, which are directly associated with hematopoietic differentiation and development, have been repeatedly and significantly associated with childhood ALL. The heterozygous genotype in ARID5B (RefSNP: rs10821936) increased the risk for leukemia with MLL-rearrangement. In particular, single nucleotide polymorphisms of ARID5B conferred increased risk for MLL-MLLT3/AF9. Based on these findings, the authors propose that while the presence of reciprocal MLL alleles has been detected in this patient, different pathological disease mechanisms may be at play due to individual recombination events.

Does voluntary hypoventilation during exercise impact EMG activity?

It has been reported that exercise under hypoxic conditions induces reduced muscle oxygenation, which could be related to enhanced activity on electromyography (EMG). Although it has been demonstrated that exercise under conditions of voluntary hypoventilation (VH) evokes muscle deoxygenation, it is unclear whether VH during exercise impacts EMG. Seven men performed bicycle exercise for 5 min at 65 % of peak oxygen uptake with normal breathing (NB) and VH. Muscle oxygenation; concentration changes in oxyhemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb) and total hemoglobin (Total-Hb); and surface EMG in the vastus lateralis muscle were simultaneously measured. In the VH condition, Oxy-Hb was significantly lower and Deoxy-Hb was significantly higher compared to those in the NB condition (P < 0.05 for both), whereas there was no significant difference in Total-Hb between the two conditions. We observed significantly higher values (P < 0.05) on integrated EMG during exercise under VH conditions compared to those under NB conditions. This study suggests that VH during exercise augments EMG activity.