A girl with membranous nephropathy associated with ventriculoperitoneal shunt infection.

Glomerulopathy associated with shunt infection is commonly membranoproliferative glomerulonephritis, whereas the causative organisms of secondary membranous nephropathy are usually viruses. We report a case of membranous nephropathy associated with shunt infection. The patient was born at 29-week gestation with a birth weight of 1178 g. Ventriculoperitoneal shunt surgery had been performed for congenital hydrocephalus. Thereafter, she had experienced seven shunt infections. At the age 13 years, proteinuria was detected in a school urinary screening. Urinalysis at our hospital demonstrated 3 + protein and 3 + blood. Laboratory testing demonstrated a serum creatinine 0.5 m/dl, albumin 2.5 g/dl, C-reactive protein (CRP) 13.7 mg/dl, and C3 182 mg/dl. Prior to repeat urinalysis, the patient developed vomiting and was admitted with suspected shunt infection. On admission, her body temperature was 36.0 ºC. Physical examination was unremarkable other than small stature and a palpable mass in the left upper quadrant. Urinalysis demonstrated 2 + protein and 1 + blood with no cells or casts. The urinary protein excretion was 3 g/day. Abnormal laboratory tests included erythrocyte sedimentation rate 102 mm/hr, CRP 11.67 mg/dl, IgG 2442 mg/dl, C3 177 mg/dl, and C4 44 mg/dl. Antibiotic therapy was initiated for a presumptive diagnosis of shunt infection and the shunt catheter was removed. Cultures obtained after antibiotic administration were negative. Proteinuria persisted after control of the shunt infection. Histology of a renal biopsy demonstrated membranous nephropathy with diffuse granular IgG staining and subepithelial deposits. Three possible pathomechanisms for her membranous nephropathy were considered.

Trends in effectiveness of inactivated influenza vaccine in children by age groups in seven seasons immediately before the COVID-19 era.

BACKGROUND: We have reported the vaccine effectiveness of inactivated influenza vaccine in children aged 6 months to 15 years between the 2013/14 and 2018/19 seasons. Younger (6-11 months) and older (6-15 years old) children tended to have lower vaccine effectiveness. The purpose of this study is to investigate whether the recent vaccine can be recommended to all age groups. METHODS: The overall adjusted vaccine effectiveness was assessed from the 2013/14 until the 2020/21 season using a test-negative case-control design based on rapid influenza diagnostic test results. Vaccine effectiveness was calculated by influenza type and by age group (6-11 months, 1-2, 3-5, 6-12, and 13-15 years old) with adjustments including influenza seasons. RESULTS: A total of 29,400 children (9347, 4435, and 15,618 for influenza A and B, and test-negatives, respectively) were enrolled. The overall vaccine effectiveness against influenza A, A(H1N1)pdm09, and B was significant (44% [95% confidence interval (CI), 41-47], 63% [95 %CI, 51-72], and 37% [95 %CI, 32-42], respectively). The vaccine was significantly effective against influenza A and B, except among children 6 to 11 months against influenza B. The age group with the highest vaccine effectiveness was 1 to 2 years old with both influenza A and B (60% [95 %CI, 55-65] and 52% [95 %CI, 41-61], respectively). Analysis for the 2020/21 season was not performed because no cases were reported. CONCLUSIONS: This is the first report showing influenza vaccine effectiveness by age group in children for several seasons, including immediately before the coronavirus disease (COVID-19) era. The fact that significant vaccine effectiveness was observed in nearly every age group and every season shows that the recent vaccine can still be recommended to children for the upcoming influenza seasons, during and after the COVID-19 era.

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.

Efficacy and safety of intravenous immunoglobulin plus prednisolone therapy in patients with Kawasaki disease (Post RAISE): a multicentre, prospective cohort study.

BACKGROUND: The RAISE study showed that additional prednisolone improved coronary artery outcomes in patients with Kawasaki disease at high risk of intravenous immunoglobulin (IVIG) resistance. However, no studies have been done to test the steroid regimen used in the RAISE study. We therefore aimed to verify the efficacy and safety of primary IVIG plus prednisolone. METHODS: We did a multicentre, prospective cohort study at 34 hospitals in Japan. We included patients diagnosed with Kawasaki disease according to the Japanese diagnostic criteria, and excluded those who were treated at other hospitals before being transferred to a participating hospital. Patients who were febrile at diagnosis received primary IVIG (2 g/kg per 24 h) and oral aspirin (30 mg/kg per day) until the fever resolved, followed by oral aspirin (5 mg/kg per day) for 2 months after Kawasaki disease onset. We stratified patients using the Kobayashi score into predicted IVIG non-responders (Kobayashi score ≥5) or predicted IVIG responders (Kobayashi score <5). For predicted non-responders, each hospital independently decided whether to add prednisolone (intravenous injection of 2 mg/kg per day for 5 days) to the primary IVIG treatment, according to their respective treatment policy, and we further divided these patients based on the primary treatment received. The primary endpoint was the incidence of coronary artery abnormalities determined by two-dimensional echocardiography at 1 month after the primary treatment in predicted non-responders treated with primary IVIG plus prednisolone. Coronary artery abnormalities were defined according to the criteria of the Japanese Ministry of Health and Welfare and of the American Heart Association (AHA). This study is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000007133. FINDINGS: From July 1, 2012, to June 30, 2015, we enrolled 2628 patients with Kawasaki disease, of whom 724 (27·6%) were predicted IVIG non-responders who received IVIG plus prednisolone as primary treatment. 132 (18·2%) of 724 patients did not respond to primary treatment. Among patients with complete data, coronary artery abnormalities were present in 40 (incidence rate 5·9%, 95% CI 4·3-8·0) of 676 patients according to the AHA criteria or in 26 (3·8%, 2·5-5·6) of 677 patients according to the Japanese criteria. Serious adverse events were reported in 12 (1·7%) of 724 patients treated with primary IVIG plus prednisolone; two of these patients had hypertension and bacteraemia that was probably related to prednisolone. One patient died possibly due to severe inflammation from the Kawasaki disease itself. INTERPRETATION: Primary IVIG plus prednisolone therapy in this study had an effect similar to that seen in the RAISE study in reducing the non-response rate and decreasing the incidence of coronary artery abnormalities. A primary IVIG and prednisolone combination therapy might prevent coronary artery abnormalities and contribute to lowering medical costs. FUNDING: Tokyo Metropolitan Government Hospitals and the Japan Kawasaki Disease Research Center.

Nebulized hypertonic saline in infants hospitalized with moderately severe bronchiolitis due to RSV infection: A multicenter randomized controlled trial.

INTRODUCTION: The efficacy of nebulized hypertonic saline (HS) therapy for shortening hospital length of stay (LOS) or improving bronchiolitic symptoms remains controversial. Most studies enrolled small numbers of subjects and did not consider the role of respiratory syncytial virus (RSV), the most common cause of acute bronchiolitis. Our aim was to evaluate the efficacy and safety of nebulized HS therapy for acute bronchiolitis due to RSV in moderately ill hospitalized infants. MATERIALS AND METHODS: This was an open-label, multicenter, randomized controlled trial comparing a nebulized HS treatment group with a normal saline (NS) group. The subjects, 128 infants with bronchiolitis due to RSV, were admitted to five hospitals in Tokyo, Japan. Three-percent HS or NS was administered via bronchodilator four times daily post-admission. The primary outcome was LOS, defined as the time until the patients fulfilled the discharge criteria, namely, absence of fever, no need for supplemental oxygen, and adequate feeding. Survival analysis was conducted in accordance with the intention-to-treat principle. RESULTS: The baseline characteristics were similar between the two groups. There was no significant overall difference in LOS between the groups (4.81 ± 2.14 days in HS vs 4.61 ± 2.18 days in NS; P = 0.60). Survival analysis by log-rank test also showed no significance (P = 0.62). Multivariate adjustment did not significantly alter the results. The treatment was well-tolerated, with no adverse effects attributable to the use of HS. CONCLUSIONS: Nebulized HS therapy did not significantly reduce LOS among infants with bronchiolitis due to RSV.