A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport's syndrome.

Children with Alport syndrome develop renal failure early in life. Since the safety and efficacy of preemptive nephroprotective therapy are uncertain we conducted a randomized, placebo-controlled, double-blind trial in 14 German sites of pediatric patients with ramipril for three to six years plus six months follow-up to determine these parameters. Pretreated children and those whose parents refused randomization became an open-arm control, which were compared to prospective real-world data from untreated children.

Twelve-month outcome in juvenile proliferative lupus nephritis: results of the German registry study.

Background: Children presenting with proliferative lupus nephritis (LN) are treated with intensified immunosuppressive protocols. Data on renal outcome and treatment toxicity is scare.

Methods: Twelve-month renal outcome and comorbidity were assessed in 79 predominantly Caucasian children with proliferative LN reported to the Lupus Nephritis Registry of the German Society of Paediatric Nephrology diagnosed between 1997 and 2015.

Infants Diagnosed with Spinal Muscular Atrophy and 4 SMN2 Copies through Newborn Screening - Opportunity or Burden?

Although the value of newborn screening (NBS) for early detection and treatment opportunity in SMA patients is generally accepted, there is still an ongoing discussion about the best strategy in children with 4 and more copies of the SMN2 gene. This gene is known to be the most important but not the only disease modifier.In our SMA-NBS pilot project in Germany comprising 278,970 infants screened between January 2018 and November 2019 were 38 positive cases with a homozygous SMN1 deletion.

Tyrphostin AG490 reduces inflammation and fibrosis in neonatal obstructive nephropathy.

Background: Congenital obstructive nephropathy is the main cause of end-stage renal disease in infants and children. Renal insufficiency is due to impaired growth and maturation in the developing kidney with obstruction. Congenital obstructive nephropathy leads to cytokine mediated inflammation and the development of interstitial fibrosis.

Neonatal obstructive nephropathy induces necroptosis and necroinflammation.

Urinary tract obstruction during kidney development causes tubular apoptosis, tubular necrosis, and interstitial inflammation. Necroptosis is a subtype of programmed necrosis mediated by the receptor-interacting serine/threonine-protein kinase-3 (RIPK3) and the pseudokinase mixed lineage kinase domain-like (MLKL). Necrosis induces inflammation and stimulates cell death in an autoamplification loop named necroinflammation.

Homoplasmy of the Mitochondrial DNA Mutation m.616T>C Leads to Mitochondrial Tubulointerstitial Kidney Disease and Encephalopathia.

Autosomal-dominant tubulointerstitial kidney disease -(ADTKD) describes tubulointerstitial kidney disease with autosomal-dominant inheritance. In 2017, the term mitochondrial tubulointerstitial kidney disease (MITKD) was introduced for tubulointerstitial kidney disease caused by mitochondrial DNA (mtDNA) mutations. To date, there are few mutations described in literature causing MITKD, one of them is m.

Molecular based newborn screening in Germany: Follow-up for cystinosis.

Background: Newborn screening (NBS) programs for treatable metabolic disorders have been enormously successful, but molecular-based screening has not been broadly implemented so far.

Methods: This prospective pilot study was performed within the German NBS framework. DNA, extracted from dried blood cards was collected as part of the regular NBS program.

Use of impregnated catheters to decrease colonization rates in neonates - A randomized controlled pilot trial.

Objective: Nosocomial infections increase mortality and morbidity in preterm infants. Central venous line colonization is a major risk factor for the development of such infections. In adults and children, antibiotic and antimycotic impregnated catheters have been demonstrated to reduce colonization.

One Year of Newborn Screening for SMA - Results of a German Pilot Project.

Objective: Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. The study was conducted to assess the impact of early detection of SMA by newborn screening (NBS) on the clinical course of the disease.

Methods: Screening was performed in two federal states of Germany, Bavaria and North Rhine Westphalia, between January 2018 and February 2019.

Multidisciplinary long-term care and modern surgical treatment of congenital melanocytic nevi - recommendations by the CMN surgery network.

In recent years, our knowledge of congenital melanocytic nevi (CMN) has greatly expanded. This has led to a paradigm shift. The present article represents a commentary by an interdisciplinary group of physicians from German-speaking countries with extensive experience in long-term care and surgical treatment of children and adults with CMN (CMN surgery network, "Netzwerk Nävuschirurgie", NNC).

Designing clinical trials in paediatric inflammatory bowel diseases: a PIBDnet commentary.

Introduction: The optimal trial design for assessing novel therapies in paediatric IBD (PIBD) is a subject of intense ongoing global discussions and debate among the different stakeholders. However, there is a consensus that the current situation in which most medications used in children with IBD are prescribed as off-label without sufficient paediatric data is unacceptable. Shortening the time lag between adult and paediatric approval of drugs is of the upmost importance.

SACS variants are a relevant cause of autosomal recessive hereditary motor and sensory neuropathy.

Mutations in the SACS gene have been initially reported in a rare autosomal recessive cerebellar ataxia syndrome featuring prominent cerebellar atrophy, spasticity and peripheral neuropathy as well as retinal abnormalities in some cases (autosomal recessive spastic ataxia of Charlevoix-Saguenay, ARSACS). In the past few years, the phenotypic spectrum has broadened, mainly owing to the availability and application of high-throughput genetic testing methods. We identified nine patients (three sib pairs, three singleton cases) with isolated, non-syndromic hereditary motor and sensory neuropathy (HMSN) who carried pathogenic SACS mutations, either in the homozygous or compound heterozygous state.

Pattern of myogenesis and vascular repair in early and advanced lesions of juvenile dermatomyositis.

Regenerative processes that counteract perifascicular muscle atrophy and capillary loss in juvenile dermatomyositis (JDM) are not well characterized. We aimed to analyze the pattern of myo-regeneration in relation to vascular damage and repair in muscle specimens from JDM patients. Myogenic regulatory factors that are sequentially expressed during myogenesis were studied by immunohistochemistry.

Associations of Maternal Diabetes During Pregnancy with Overweight in Offspring: Results from the Prospective TEDDY Study.

Objective: This study aimed to determine the relationship between different forms of, and potential pathways between, maternal diabetes and childhood obesity at different ages.

Methods: Prospective cohort data from The Environmental Determinants of Diabetes in the Young (TEDDY) study, which was composed of 5,324 children examined from 0.25 to 6 years of age, were analyzed.

Clinical benefits of introducing real-time multiplex PCR for cerebrospinal fluid as routine diagnostic at a tertiary care pediatric center.

Background: Sepsis-like illness with suspected meningitis or encephalitis is a common reason for using empiric antimicrobial therapy in infants and children. However, in cases of viral meningitis not covered by these antimicrobials, this management is ineffective and due to side effects potentially harmful.

Methods: A retrospective analysis of cerebrospinal fluid (CSF) multiplex PCRs (Biofire FilmArray) in children with clinical suspicion of meningitis, encephalitis or sepsis-like illness was performed over the period of 1 year.

Novel SBF2 mutations and clinical spectrum of Charcot-Marie-Tooth neuropathy type 4B2.

Biallelic SBF2 mutations cause Charcot-Marie-Tooth disease type 4B2 (CMT4B2), a sensorimotor neuropathy with autosomal recessive inheritance and association with glaucoma. Since the discovery of the gene mutation, only few additional patients have been reported. We identified seven CMT4B2 families with nine different SBF2 mutations.

PRUNE1 Deficiency: Expanding the Clinical and Genetic Spectrum.

Background: Primary microcephaly and profound global developmental delay have been considered the core clinical phenotype in patients with bi-allelic mutations.

Methods: Linkage analysis and whole-exome sequencing (WES) in a multiplex family and extraction of further cases from a WES repository containing 571 children with severe developmental disabilities and neurologic symptoms.

Results: We identified bi-allelic mutations in twelve children from six unrelated families.

Cyclosporine A responsive congenital nephrotic syndrome with single heterozygous variants in NPHS1, NPHS2, and PLCE1.

Background: Congenital nephrotic syndrome (CNS) is primarily a monogenetic disease, with the majority of cases due to changes in five different genes: the nephrin (NPHS1), podocin (NPHS2), Wilms tumor 1 (WT1), laminin ß2 (LAMB2), and phospholipase C epsilon 1 (PLCE1, NPHS3) gene. Usually CNS is not responsive to immunosuppressive therapy, but treatment with ACE inhibitors, AT1 receptor blockade and/or indomethacin can reduce proteinuria. If the disease progresses to end-stage renal disease, kidney transplantation is the therapy of choice.

Duration to Establish an Emergency Vascular Access and How to Accelerate It: A Simulation-Based Study Performed in Real-Life Neonatal Resuscitation Rooms.

Objectives: To compare the duration to establish an umbilical venous catheter and an intraosseous access in real hospital delivery rooms and as a secondary aim to assess delaying factors during establishment and to provide recommendations to accelerate vascular access in neonatal resuscitation.

Design: Retrospective analysis of audio-video recorded neonatal simulation training.

Settings: Simulation training events in exact replications of actual delivery/resuscitation rooms of 16 hospitals with different levels of care (Austria and Germany).

Identification of co-occurrence in a patient with Dent's disease and ADA2-deficiency by exome sequencing.

Patients with co-occurrence of two independent pathologies pose a challenge for clinicians as the phenotype often presents as an unclear syndrome. In these cases, exome sequencing serves as a powerful instrument to determine the underlying genetic causes. Here, we present the case of a 4-year old boy with proteinuria, microhematuria, hypercalciuria, nephrocalcinosis, livedo-like rash, recurrent abdominal pain, anemia and continuously elevated CRP.

Magnetic Resonance Enterography Cannot Replace Upper Endoscopy in Pediatric Crohn Disease: An Imagekids Sub-study.

Objectives: Although magnetic resonance enterography (MRE) can accurately reflect ileal inflammation in pediatric Crohn disease (CD), there are no pediatric data on the accuracy of MRE to detect upper gastrointestinal tract (UGI) lesions. We aimed to compare MRE and esophagogastroduodenoscopy (EGD) in detecting the spectrum and severity of UGI disease in children.

Methods: This is an ancillary study of the prospective multi-center ImageKids study focusing on pediatric MRE.

Cesarean Section on the Risk of Celiac Disease in the Offspring: The Teddy Study.

Objective: Cesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort.

Methods: From 2004 to 2010, infants from the general population who tested positive for HLA DR3-DQ2 or DR4-DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study.

Intake of Energy and Protein is Associated with Overweight Risk at Age 5.5 Years: Results from the Prospective TEDDY Study.

Objective: The associations of energy, protein, carbohydrate, and fat intake with weight status up to the age of 5.5 years were prospectively assessed in The Environmental Determinants of Diabetes in the Young (TEDDY) study.

Methods: Food record data (over 3 days) and BMI measurements between 0.