An international, multi-center study evaluated rituximab therapy in childhood steroid-resistant nephrotic syndrome.

The efficacy and safety of rituximab in childhood steroid-resistant nephrotic syndrome (SRNS) remains unclear. Therefore, we conducted a retrospective cohort study at 28 pediatric nephrology centers from 19 countries in Asia, Europe, North America and Oceania to evaluate this. Children with SRNS treated with rituximab were analyzed according to the duration of calcineurin inhibitors (CNIs) treatment before rituximab [6 months or more (CNI-resistant) and under 6 months]. Primary outcome was complete/partial remission (CR/PR) as defined by IPNA/KDIGO guidelines. Secondary outcomes included kidney failure and adverse events. Two-hundred-forty-six children (mean age, 6.9 years; 136 boys; 57% focal segmental glomerulosclerosis, FSGS) were followed a median of 32.4 months after rituximab. All patients were in non-remission before rituximab. (146 and 100 children received CNIs for 6 month or more or under 6 months before rituximab, respectively). In patients with CNI-resistant SRNS, the remission rates (CR/PR) at 3-, 6-, 12- and 24-months were 26% (95% confidence interval 19.3-34.1), 35.6% (28.0-44.0), 35.1% (27.2-43.8) and 39.1% (29.2-49.9), respectively. Twenty-five patients were in PR at 12-months, of which 22 had over 50% reduction in proteinuria from baseline. The remission rates among children treated with CNIs under 6 months before rituximab were 42% (32.3-52.3), 52% (41.8-62.0), 54% (44.3-64.5) and 60% (47.6-71.3) at 3-, 6-, 12-, and 24-months. Upon Kaplan-Meier analysis, non-remission and PR at 12-months after rituximab, compared to CR, were associated with significantly worse kidney survival. Adverse events occurred in 30.5% and most were mild. Thus, rituximab enhances remission in a subset of children with SRNS, is generally safe and CR following rituximab is associated with favorable kidney outcome.

Transient immune deficiency accompanied with homozygous CBL rare variant.

BACKGROUND: A critical role in cellular proliferation is played by Casitas B-lineage Lymphoma proto-oncogene (CBL). Germline heterozygous CBL variants give rise to CBL syndrome, which is phenotypically similar to RASopathy. Somatic mutations in CBL have been reported in patients with juvenile myelomonocytic leukemia (JMML). METHODS: Exome analysis was performed in a patient with immunodeficiency who developed Pneumocystis jirovecii pneumonia. RESULTS: Exome analysis identified a homozygous CBL missense variant. Cell biological analysis of this CBL variant confirmed attenuated function. CONCLUSION: Spontaneous regression of hematological proliferation has been observed in patients with CBL-mutated JMML and in patients with CBL syndrome. Intriguingly, immunological impairment was spontaneously ameliorated by aging in this patient.

Group A streptococcus endocarditis in children: 2 cases and a review of the literature.

BACKGROUND: Infective endocarditis (IE) is defined as endocarditis caused by microorganisms (bacteria or fungi) involving either the heart or great vessels. The clinical course of IE can be complicated by cardiac dysfunction and bacterial embolization to virtually any organ. Staphylococcus aureus and viridans group streptococci are the most common causative organisms, whereas group A Streptococcus (GAS) is less common. Although some GAS serotypes have been associated with severe disease, there are few reports of IE associated with GAS serotypes. Here, we report two cases of GAS endocarditis and review the associated literature. CASE PRESENTATIONS: Patient 1 was a previously healthy 14-year-old girl who developed bacteremia and disseminated intravascular coagulation secondary to left foot cellulitis. She was administered intravenous antibiotics. Two of three blood cultures grew Streptococcus pyogenes (T6 M6, emm6.104). Three days later, a new systolic ejection murmur was heard and echocardiography showed mitral regurgitation with mitral valve vegetation. Because of the resultant severity of the mitral regurgitation, she underwent mitral valve repair after 10 weeks of antibiotic treatment. Patient 2 was a 17-month old boy who presented with a fever. He had a history of spontaneous closure of a ventricular septal defect (VSD). He was started on intravenous antibiotics for possible bacteremia. Two consecutive blood cultures with an interval of more than 12 h grew S. pyogenes (T4 M4, emm4.0). Five days later, echocardiography showed vegetation on a membranous ventricular septal aneurysm. The patient responded well to antibiotics, and recovered fully with no complications. CONCLUSIONS: Although both patients developed GAS endocarditis, patient 1 did not have any predisposing conditions for IE, and patient 2 had a only a low-risk predisposing condition, a VSD that had closed spontaneously at five months of age. We found twelve reports in the literature of GAS endocarditis with information on serotypes. All patients in these reports had GAS endocarditis caused by serotypes generally associated with milder infections, but no specific risk trends were identified. A greater accumulation of cases is necessary to more clearly elucidate the association between GAS IE and specific serotypes.

Ultrasound-guided peripheral intravenous access placement for children in the emergency department.

The usefulness of ultrasound guidance in peripheral intravenous access placement has yet to be established in children. In this prospective comparative study, we investigated success rates of intravenous access placement with ultrasound guidance in a pediatric emergency department. After a failed first attempt with the conventional technique, the second and third attempts were conducted using either the ultrasound guidance (a real-time, dual operator method) or the conventional technique. The success rates within the two interventional attempts were then compared. From a total of 712 participants, those with a failed first attempt were allocated to the ultrasound guidance (n = 99) and conventional technique (n = 100) groups. The success rate was significantly lower for the ultrasound guidance (65%) than for the conventional technique (84%) group (p = 0.002, chi-square test). This remained significant after adjusting for confounders with multiple logistic regression analysis (odds ratio 2.60, 95% confidence interval 1.26-5.37, p = 0.001). CONCLUSION: Ultrasound-guided intravenous access placement using a real-time, dual operator method led to a significantly lower success rate than the conventional technique in children with one failed conventional attempt in the emergency department. TRIAL REGISTRATION: UMIN000014730 What is Known: • Children experience a low success rate (about 60% with 1 attempt and about 90% with 4 attempts) for IV access placement. • Ultrasound guidance may lead to a decreased number of attempts and shorter procedural time with comparable overall IV success rate. What is New: • Ultrasound-guided IV placement (a real-time, dual operator method) actually led to a significantly lower IV success rate than the conventional technique in children in the emergency department. • Our result warrants further trials to determine the precise population who benefits from ultrasound guidance.

Repeated ultrasound tests could be used to identify an isolated gastric duplication cyst before surgery.

A toddler girl was diagnosed with intra-abdominal simple cyst in the splenic flexure at the gestational period. Due to a severe fever that persisted for 6 days, she was admitted to the emergency room. The diagnosis of intraperitoneal cyst infection was made after contrast-enhanced CT revealed an enlarged cyst and a heterogeneous contrast effect on the cyst wall. A double-wall sign was observed on the cyst wall during continuous ultrasound follow-up, which led to the preoperative diagnosis of the cyst as a duplication cyst. The double-wall sign and cyst peristalsis were identified via successive ultrasound examinations to support the cyst diagnosis. Identifying a duplication cyst based solely on symptoms alone is difficult because the condition may present in different ways.

Advantages of monitoring rT3 and dividing LT3 dose in the treatment of consumptive hypothyroidism associated with infantile hepatic hemangioma.

OBJECTIVES: In consumptive hypothyroidism associated with infantile hepatic hemangiomas (IHH), elevated reverse triiodothyronine (rT3) is known due to elevated D3. This report shows that rT3 is a new indicator of IHH progression and that three divided doses of LT3 per day were more effective than a single dose. CASE PRESENTATION: A 23 day-old boy was diagnosed with diffuse IHH and severe hypothyroidism with high rT3. Propranolol and LT4 were administered. Hemangiomas gradually diminished and rT3 decreased, but the thyroid-stimulating hormone remained elevated, and free triiodothyronine (fT3) did not normalize after 2 weeks of treatment. Liothyronine (LT3) was started as a single dose and then divided into three doses after 1 week, which stabilized thyroid function. CONCLUSIONS: rT3 levels were less variable and decreased in conjunction with tumor shrinkage; thus, rT3 is an indicator of therapeutic outcomes for IHH. LT3 administered in divided doses aided in managing IHH-associated hypothyroidism.

Case of Infantile Legionella Pneumonia After Bathing in Reheated and Reused Water.

A 1-month-old girl developed respiratory failure due to bilateral interstitial pneumonia after bathing in reheated and reused water. A molecular test for sputum and an environmental culture detected Legionella pneumophila serotype 1. This is the first report of infantile legionellosis contracted from a bathtub at home.

Childhood leptospirosis in an industrialized country: Population-based study in Okinawa, Japan.

Leptospirosis is considered underdiagnosed because of its nonspecific presentation and lack of proper understanding of its epidemiology. Early diagnosis and treatment are crucial. However, few data are available on confirmed leptospirosis cases in children in industrialized countries. We therefore aimed to describe epidemiologic and clinical characteristics of laboratory-confirmed childhood leptospirosis in Okinawa, Japan. We reviewed the national surveillance data of pediatric leptospirosis in Okinawa, Japan from January 2003 through December 2015. The database included all of laboratory-confirmed leptospirosis diagnosed at the only central laboratory for leptospirosis in the region. There were 44 children (0-20 years of age) with laboratory-confirmed leptospirosis. Of these, 90% were male, 91% were 10-20 years of age, and 96% of cases occurred in August and September. The number of laboratory-confirmed patients ranged from 0 to 11 per year (mean: 3.3 per year), and the estimated annual rate was 1.0 per 100,000 pediatric populations. In all cases, the presumed infection route was recreational exposure to river water. Commonly observed manifestations include fever (95%), myalgia (52%), and conjunctival suffusion (52%). Childhood leptospirosis in Okinawa, Japan occurred predominantly in teenage boys after freshwater exposure in summer, and most patients had characteristic conjunctival suffusion. Cohort studies would be helpful to better understand more detailed clinical manifestations in association with prognosis.

Five cases of childhood-onset Graves' disease treated with either surgery or radio-iodine therapy.

There are three major therapeutic options for the treatment of Graves' disease (GD): antithyroid drugs (ATDs), thyroidectomy, and radio-iodine (RAI) therapy. ATDs are the initial treatment option for children. However, some pediatric GD patients who are initially treated with ATDs require other type of treatments later on. We reviewed the medical records of childhood-onset GD cases retrospectively to report the clinical course of patients who received either surgery or RAI therapy subsequent to treatment with ATDs. Childhood-onset GD was successfully managed in five girls with non-ATD treatments at the age of 7-14 yr following an unfavorable outcome of initial ATD treatment. Four cases had surgery and one case was managed with RAI therapy. The reasons for switching to non-ATD treatment included poor compliance, failure to maintain remission, serious adverse events resulting from ATDs, and religious background. In conclusion, surgery and RAI therapy could be good alternative treatment options for children with GD.