A Novel AICDA Splice-Site Mutation in Two Siblings with HIGM2 Permits Somatic Hypermutation but Abrogates Mutational Targeting.

Hyper-IgM syndrome type 2 (HIGM2) is a B cell intrinsic primary immunodeficiency caused by mutations in AICDA encoding activation-induced cytidine deaminase (AID) which impair immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM). Whereas autosomal-recessive AID-deficiency (AR-AID) affects both CSR and SHM, the autosomal-dominant form (AD-AID) due to C-terminal heterozygous variants completely abolishes CSR but only partially affects SHM. AR-AID patients display enhanced germinal center (GC) reactions and autoimmune manifestations, which are not present in AD-AID, suggesting that SHM but not CSR regulates GC reactions and peripheral B cell tolerance.

Low-grade diffusely infiltrative tumour (LGDIT), SMARCB1-mutant: A clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC.

Low-grade diffusely infiltrative tumour (LGDIT), SMARCB1-mutant, is a histopathological distinct low-grade lesion encountered in older children and young adults that shows epigenetic similarity with ATRT-MYC and has the potential for malignant progression.

Unsuccessful mid-term results for distal humeral hemiepiphysiodesis to treat cubitus varus deformity in young children.

Cubitus varus is the most common complication following a pediatric humeral supracondylar fracture. No reports are available on the result of hemiepiphysiodesis to correct this deformity. We report the use of a transphyseal crossed cannulated screw (Metaizeau technique) in five very young children (mean 3 years and 7 months).

Home-hospital care for children with acute illnesses: A 2-year follow-up study.

Aim: Procedures normally performed in the hospital setting are increasingly delivered as part of hospital at home (HAH) programmes. The aim of this study is to describe the procedures and diseases treated during the first 2 years of a new paediatric HAH programme.

Methods: This is a retrospective, observational study conducted in the HAH programme of Niño Jesús Children's Hospital (Spain).

A disorder clinically resembling cystic fibrosis caused by biallelic variants in the gene.

Purpose: We sought to describe a disorder clinically mimicking cystic fibrosis (CF) and to elucidate its genetic cause.

Methods: Exome/genome sequencing and human phenotype ontology data of nearly 40 000 patients from our Bio/Databank were analysed. RNA sequencing of samples from the nasal mucosa from patients, carriers and controls followed by transcriptome analysis was performed.

Paediatric Strategy Forum for medicinal product development of chimeric antigen receptor T-cells in children and adolescents with cancer: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

The seventh multi-stakeholder Paediatric Strategy Forum focused on chimeric antigen receptor (CAR) T-cells for children and adolescents with cancer. The development of CAR T-cells for patients with haematological malignancies, especially B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), has been spectacular. However, currently, there are scientific, clinical and logistical challenges for use of CAR T-cells in BCP-ALL and other paediatric malignancies, particularly in acute myeloid leukaemia (AML), lymphomas and solid tumours.

Cui Bono? Identifying Patient Groups That May Benefit From Granulocyte Transfusions in Pediatric Hematology and Oncology.

Introduction: Granulocyte transfusions have long been used to bridge the time to neutrophil recovery in patients with neutropenia and severe infection. Recent randomized controlled trials did not prove a beneficial effect of granulocyte transfusions, but were likely underpowered and suffered from very heterogeneous study populations.

Methods: We retrospectively reviewed data of all patients treated with granulocyte transfusions at our pediatric center from 2004 to 2019.

Infantile myofibromatosis: Excellent prognosis but also rare fatal progressive disease. Treatment results of five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry.

Background: Infantile myofibromatosis (IM) is a rare benign soft tissue tumor and often a self-limiting disease but rarely includes life-threatening complications. Little is known about optimal treatment of primary localized (LD) and multifocal disease (MFD).

Methods: Treatment and outcome of 95 children with IM registered within five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry (1981-2016) were evaluated.

Effects of exercise training on heart rate variability in children and adolescents with pulmonary arterial hypertension: a pilot study.

Background: Pulmonary arterial hypertension (PAH) is often associated with cardiac autonomic dysfunction, and heart rate variability (HRV) as marker of cardiac autonomic function is even related to disease severity. Knowledge about the effects of physical activity on HRV is limited in these patients. We aimed to assess whether HRV parameters can be influenced by a supervised exercise training program and whether respective changes are related to levels of activity.

Glenohumeral abduction contractures after residual neonatal brachial plexus injury.

Glenohumeral abduction contractures are common in patients with neonatal brachial plexus injury, but little has been previously published about them. We conducted a retrospective analysis of data prospectively collected from 205 consecutive children (108 female) of mean age 9.6 years with neonatal brachial plexus injury (C5-C6, 58%; C5-C7, 29%; C5-T1, 14%).

Efficacy and safety of ketogenic dietary theraphies in infancy. A single-center experience in 42 infants less than two years of age.

Purpose: Ketogenic dietary therapies (KDT) are high-fat and low-carbohydrate diets that may achieve seizure control and improve cognitive state. We describe our KDT experience in infants (children less than two years of age).

Research Methods & Procedures: We conducted a retrospective, descriptive and observational study of 42 infants treated with KDT between 2000-2018.

Update on sacral neuromodulation and overactive bladder in pediatrics: A systematic review.

Objectives: Sacral electrical stimulation has been used for more than a century as an alternative therapy for adult urinary syndromes. In the literature, several studies have validated the efficacy of this technique based on clinical and urodynamic criteria. Nevertheless, few studies have shown beneficial results in children with overactive bladder.

Pooled RT-qPCR testing for SARS-CoV-2 surveillance in schools - a cluster randomised trial.

Background: The extent to which children and adolescents contribute to SARS-CoV-2 transmission remains not fully understood. Novel high-capacity testing methods may provide real-time epidemiological data in educational settings helping to establish a rational approach to prevent and minimize SARS-CoV-2 transmission. We investigated whether pooling of samples for SARS-CoV-2 detection by RT-qPCR is a sensitive and feasible high-capacity diagnostic strategy for surveillance of SARS-CoV-2 infections in schools.

Age, American Thyroid Association Risk Group, and Response to Therapy Are Prognostic Factors in Children With Differentiated Thyroid Cancer.

Context: Against the background of increasing incidence, pediatric differentiated thyroid carcinoma (DTC) frequently presents with advanced disease and high recurrence rates while prognosis remains excellent.

Background: We investigated the use of a pediatric classification and an adult response to therapy risk stratification for pediatric DTC patients and their implications for adaptation of treatment and follow-up.

Methods: Data from patients aged <18 years with a diagnosis of primary DTC, registered with the German Pediatric Oncology Hematology-Malignant Endocrine Tumor registry since 1995, were analyzed.

New aspects and innovations in the local treatment of renal and urogenital pediatric tumors.

Local treatment plays a key role for patients' outcome in tumors of the urogenital tract in children. Despite a great variety of different etiologies, the specific localization of pediatric urogenital tumors renders several characteristic demands to the treating personnel. Surgery and radiotherapy are the main elements of local treatment in this group of neoplasms.

Non-Animal Stabilized Hyaluronic Acid/Dextranomer Gel (NASHA/Dx, Deflux) for Endoscopic Treatment of Vesicoureteral Reflux: What Have We Learned Over the Last 20 Years?

Non-animal stabilized hyaluronic acid/dextranomer gel (Deflux; NASHA/Dx) was developed as a treatment for vesicoureteral reflux (VUR) in the 1990s. To mark 20 years since the US approval of this agent, we reviewed its properties, best practice for application, and the available clinical safety and efficacy data. Long-term or randomized, controlled studies of treatment with NASHA/Dx have reported VUR resolution rates of 59%-100% with low rates of febrile urinary tract infection post-treatment (4%-25%), indicating long-term protection of the kidneys.

Efficacy, Retention and Tolerability of Everolimus in Patients with Tuberous Sclerosis Complex: A Survey-Based Study on Patients' Perspectives.

Background: The approval of everolimus (EVE) for the treatment of angiomyolipoma (2013), subependymal giant cell astrocytoma (2013) and drug-refractory epilepsy (2017) in patients with tuberous sclerosis complex (TSC) represents the first disease-modifying treatment option available for this rare and complex genetic disorder.

Objective: The objective of this study was to analyse the use, efficacy, tolerability and treatment retention of EVE in patients with TSC in Germany from the patient's perspective.

Methods: A structured cross-age survey was conducted at 26 specialised TSC centres in Germany and by the German TSC patient advocacy group between February and July 2019, enrolling children, adolescents and adult patients with TSC.

Free vascularized iliac periosteal graft for bilateral forearm nonunion reconstruction in a child with bilateral transfemoral amputation.

Vascularized periosteal flaps have been reported as very effective for treating biologically complex bone nonunion in pediatric patients, owing to their high angiogenic and osteogenic potentials. The purpose of this article is to report a case of a 6-year-old patient with nonunion involving both forearms and a very limited bone flap donor site in the context of prior bilateral transfemoral amputation due to meningococcal sepsis. Two free vascularized iliac periosteal flaps (VIPF), supplied by the deep circumflex iliac vessels, were used in two stages to reconstruct the forearms.

Transcutaneous sacral electrical stimulation versus oxibutynin for the treatment of overactive bladder in children.

Background: Nowadays there is still no ideal treatment for paediatric overactive bladder. Initial management measures (urotherapy and constipation control), resolve 40% of cases. The second line of treatment in overactive bladder is anticholinergic drugs, above all oxybutynin.

Adrenocortical tumours in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Adrenocortical tumours (ACTs) are rare during childhood. A complete surgical resection provides the best chance of cure, but the role and efficacy of the adjuvant therapy are still controversial. Various histologic criteria of malignancy for ACTs adopted in children do not facilitate comparative studies and are not completely shared.

Childhood-onset Craniopharyngioma.

Craniopharyngiomas are rare embryonic malformational tumors of the sellar/parasellar region, classified by the World Health Organization (WHO) as tumors with low-grade malignancy (WHO I). The childhood adamantinomatous subtype of craniopharyngioma is usually cystic with calcified areas. At the time of diagnosis, hypothalamic/pituitary deficits, visual disturbances, and increased intracranial pressure are major symptoms.