Are psychiatric disorders associated with thyroid hormone therapy in adolescents and young adults with type 1 diabetes?

Background: To evaluate the association between thyroid autoimmunity and psychiatric disorders (depression, anxiety, eating disorder, schizophrenia or attention-deficit/hyperactivity disorder) among adolescents and young adults with type 1 diabetes (11-25 years).

Methods: We compared 9368 type 1 diabetes patients with thyroid autoimmunity (3789 of them treated with levothyroxine) with 62 438 type 1 diabetes patients without any thyroid disease from a multicentre diabetes patient follow-up registry (DPV) in terms of psychiatric disorders. Thyroid autoimmunity was defined as documented diagnosis of Hashimoto thyroiditis or positive antibodies against thyroid peroxidase or thyroglobulin.

Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting.

PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR.

A child with soft-tissue infection and lymphadenitis.

We report a case of a soft-tissue infection with , a rare opportunistic pathogen in individuals with chronic granulomatous disease.

De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy.

Purpose: This study aims to provide a comprehensive description of the phenotypic and genotypic spectrum of SNAP25 developmental and epileptic encephalopathy (SNAP25-DEE) by reviewing newly identified and previously reported individuals.

Methods: Individuals harboring heterozygous missense or loss-of-function variants in SNAP25 were assembled through collaboration with international colleagues, matchmaking platforms, and literature review. For each individual, detailed phenotyping, classification, and structural modeling of the identified variant were performed.

Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target?

Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. More than a third of patients do not respond to standard therapy and urgently require alternative treatment options. Due to a high degree of inter- and intra-tumoural genomic heterogeneity and complexity, recurrent molecular alterations that could serve as prognostic predictors or therapeutic targets are still lacking in osteosarcoma.

Educational and knowledge gaps within the European reference network on rare endocrine conditions.

Objective: The European Reference Network on Rare Endocrine Conditions (Endo-ERN), operational since 2017, consists of 71 health care providers (HCPs) in 19 EU member states. Our objective was to assess education and knowledge on rare endocrine conditions.

Design And Methods: A survey was developed and sent through the DIGIT-EUROSURVEY system to all Endo-ERN HCPs.

Normocomplementemic Urticarial Vasculitis Associated with A/H1N1 in a Child. Case Report.

Urticarial vasculitis is an entity characterized by urticarial rashes that are typically pruritic and painful, associated with angioedema and purpura. Influenza viruses are common respiratory pathogens that can cause seasonal infections and global human morbidity/mortality. A 4.

Impact of COVID-19 in paediatric early-phase cancer clinical trials in Europe: A report from the Innovative Therapies for Children with Cancer (ITCC) consortium.

Introduction: Data regarding real-world impact on cancer clinical research during COVID-19 are scarce. We analysed the impact of the COVID-19 pandemic on the conduct of paediatric cancer phase I-II trials in Europe through the experience of the Innovative Therapies for Children with Cancer (ITCC).

Methods: A survey was sent to all ITCC-accredited early-phase clinical trial hospitals including questions about impact on staff activities, recruitment, patient care, supply of investigational products and legal aspects, between 1st March and 30th April 2020.

Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children.

The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.

Diagnostic disagreement between clinical standard histopathological- and retrospective assessment of histopathology-based gastrointestinal graft-versus-host disease in children.

Background: No previous paediatric study has evaluated the frequency of diagnostic disagreement between clinical standard histopathological assessment (CSHA) and retrospective, independent, histopathological assessment (RIHA) of gastrointestinal Graft-Versus-Host Disease (GI-GVHD) METHODS: In a retrospective cohort study, based on gastrointestinal biopsies collected from allogeneic HSCT-treated children (<18 years) with symptom-based GI-GVHD, we evaluated; disagreement of histopathology-based GI-GVHD diagnosis in CSHA vs RIHA, and potential clinical consequences of differences between the assessments. The CSHA-based diagnoses were retrieved from histopathology reports. The RIHA was performed by one pathologist, blinded to the CSHA outcomes and based on the minimal criteria for histopathology-based GI-GVHD diagnosis by the NIH 2014.

Withholding or withdrawing life-sustaining treatment in extremely low gestational age neonates.

Objective: To identify sociodemographic and clinical factors associated with withholding or withdrawing life-sustaining treatment (WWLST) for extremely low gestational age neonates.

Design: Observational study of prospectively collected registry data from 19 National Institute of Child Health and Human Development Neonatal Research Network centres on neonates born at 22-28 weeks gestation who died >12 hours through 120 days of age during 2011-2016. Sociodemographic and clinical factors were compared between infants who died following WWLST and without WWLST.

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries.

Background: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.

Methods: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.

Patient with an autosomal-recessive MBTPS1-linked phenotype and clinical features of Silver-Russell syndrome.

Pathogenic variants in the MBTPS1 gene encoding the Site 1 protease have been described so far only in one growth retarded patients with skeletal deformities, large ears, a triangular face reminiscent to Silver-Russell syndrome (SRS), and elevated blood lysosomal enzymes. We now report on the identification of a second adult patient homozygous for one of the two published pathogenic MBTPS1 variants (p.Asp365Gly) by Whole Exome Sequencing (WES), and a comparable phenotype.

A Metabolomics Workflow for Analyzing Complex Biological Samples Using a Combined Method of Untargeted and Target-List Based Approaches.

In the highly dynamic field of metabolomics, we have developed a method for the analysis of hydrophilic metabolites in various biological samples. Therefore, we used hydrophilic interaction chromatography (HILIC) for separation, combined with a high-resolution mass spectrometer (MS) with the aim of separating and analyzing a wide range of compounds. We used 41 reference standards with different chemical properties to develop an optimal chromatographic separation.

Elevated Homocysteine after Elevated Propionylcarnitine or Low Methionine in Newborn Screening Is Highly Predictive for Low Vitamin B12 and Holo-Transcobalamin Levels in Newborns.

Early diagnostics and treatment of vitamin B12 deficiency (B12D) in infants, mainly maternally conditioned, is crucial in preventing possible developmental delay and neurological deficits. Currently, B12D is rarely listed in regular newborn screening panels and mostly regarded as an incidental finding. The aim of this study was to evaluate a targeted newborn screening strategy for detection of suspected B12D.

Genotype-phenotype correlations in recessive titinopathies.

Purpose: High throughput sequencing analysis has facilitated the rapid analysis of the entire titin (TTN) coding sequence. This has resulted in the identification of a growing number of recessive titinopathy patients. The aim of this study was to (1) characterize the causative genetic variants and clinical features of the largest cohort of recessive titinopathy patients reported to date and (2) to evaluate genotype-phenotype correlations in this cohort.

Are Vascularized Periosteal Flaps Useful for the Treatment of Difficult Scaphoid Nonunion in Adults? A Prospective Cohort Study of 32 Patients.

Purpose: To evaluate clinical and radiological outcomes after surgical treatment of difficult scaphoid nonunion in adults with a vascularized thumb metacarpal periosteal pedicled flap (VTMPF).

Materials And Methods: Thirty-two patients at least 18 years old, with scaphoid nonunion and characteristics associated with a poor prognosis, who underwent a VTMPF procedure, were included in this retrospective cohort study with a mean follow-up of 17 months. Factors associated with a poor prognosis were a delay in presentation of over 5 years, the presence of avascular necrosis, and previous nonunion surgery.

New Insights into Adult and Paediatric Chronic Non-bacterial Osteomyelitis CNO.

Purpose Of Review: To describe in detail the clinical synopsis and pathophysiology of chronic non-bacterial osteomyelitis and SAPHO syndrome.

Recent Findings: Chronic non-bacterial osteomyelitis (CNO) has been identified as a disease entity for almost 50 years. This inflammatory bone disorder is characterized by osteolytic as well as hyperostotic/osteosclerotic lesions.

A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness.

Context: Individual patients vary in their response to growth hormone (GH). No large-scale genome-wide studies have looked for genetic predictors of GH responsiveness.

Objective: To identify genetic variants associated with GH responsiveness.

Constitutional mismatch repair deficiency-associated brain tumors: report from the European C4CMMRD consortium.

Background: Malignant brain tumors (BT) are among the cancers most frequently associated with constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations in mismatch repair genes. This study analyzed data from the European "Care for CMMRD" (C4CMMRD) database to describe their clinical characteristics, treatments, and outcome with the aim of improving its diagnosis/treatment.

Methods: Retrospective analysis of data on patients with CMMRD and malignant BT from the C4CMMRD database up to July 2017.

Genetic and functional insights into CDA-I prevalence and pathogenesis.

Background: Congenital dyserythropoietic anaemia type I (CDA-I) is a hereditary anaemia caused by biallelic mutations in the widely expressed genes and . Little is understood about either protein and it is unclear in which cellular pathways they participate.

Methods: Genetic analysis of a cohort of patients with CDA-I identifies novel pathogenic variants in both known causative genes.