Six molecular patterns leading to hemophilia A phenotype in 18 females from Poland.

Introduction: Female hemophilia is an intriguing rare disorder and few larger reports on its genetic etiology are available. While historically the diagnosis was satisfactorily reached by factor VIII activity assays, the clinical and potentially therapeutic heterogeneity of female hemophilia calls for comprehensive molecular diagnosis in each case. Currently, the genetic investigations are not a part of routine, state-funded, diagnostics in Poland, and thus molecular epidemiological data are missing.

Overcoming Heterogeneity of Antigen Expression for Effective CAR T Cell Targeting of Cancers.

Chimeric antigen receptor (CAR) gene-modified T cells (CAR T cells) can eradicate B cell malignancies via recognition of surface-expressed B lineage antigens. Antigen escape remains a major mechanism of relapse and is a key barrier for expanding the use of CAR T cells towards solid cancers with their more diverse surface antigen repertoires. In this review we discuss strategies by which cancers become amenable to effective CAR T cell therapy despite heterogeneous phenotypes.

Outcome of patients with Fanconi anemia developing myelodysplasia and acute leukemia who received allogeneic hematopoietic stem cell transplantation: A retrospective analysis on behalf of EBMT group.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for bone marrow failure in patients with Fanconi anemia (FA), but the presence of a malignant transformation is associated with a poor prognosis and the management of these patients is still challenging. We analyzed outcome of 74 FA patients with a diagnosis of myelodysplastic syndrome (n = 35), acute leukemia (n = 35) or with cytogenetic abnormalities (n = 4), who underwent allo-HSCT from 1999 to 2016 in EBMT network. Type of diagnosis, pre-HSCT cytoreductive therapies and related toxicities, disease status pre-HSCT, donor type, and conditioning regimen were considered as main variables potentially influencing outcome.

Pediatrician performed point-of-care ultrasound for the detection of ingested foreign bodies: case series and review of the literature.

Purpose: Foreign body (FB) ingestions represent a common problem in children. History and physical examination are commonly not enough to diagnose a foreign body ingestion; therefore, conventional radiography is routinely used to detect them. Point-of-care ultrasound is widely used in the emergency department for several diagnostic applications but there are few articles describing the possibility to use point-of-care ultrasound to detect ingested foreign bodies, and the necessary training to get competent in this application.

Quantitative signal intensity ratios to distinguish between subfascial lipoma and atypical lipomatous tumor/well-differentiated liposarcoma using short-tau inversion recovery (STIR) MRI.

Purpose: To establish simple quantitative variables at short-tau inversion recovery (STIR) magnetic resonance imaging (MRI) to identify lipomas with high specificity in patients with indeterminate subfascial lipomatous tumors.

Materials And Methods: The MRI examinations of 26 patients (14 men, 12 women; mean age 63±12.5 [SD] years; range: 40-84years) with histopathologically proven subfascial atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLs) and those of 68 patients (32 men, 36 women; mean age, 56±13.

Somatostatin receptor expression and mTOR pathway activation in glioneuronal tumours of childhood.

Purpose: To investigate the expression of somatostatin receptors (SSTRs) and markers of mTOR pathway in paediatric glioneuronal tumours and correlate these findings with tumour type, BRAFV600E mutational status and clinical characteristics such as tumour location, seizure frequency and duration, and age.

Method: 37 children and adolescents with a neuropathological diagnosis of glioneuronal tumour were identified over a 22-year period. Immunohistochemical analyses for SSTRs type 1, 2A, 3, 5 and ezrin-radixin-moesin (ERM) and phosphorylated S6 (pS6), which are indicators of mTOR pathway activation, were performed in tumour specimens from 33 patients and evaluated using the immunoreactive score (IRS).

"UniCAR"-modified off-the-shelf NK-92 cells for targeting of GD2-expressing tumour cells.

Antigen-specific redirection of immune effector cells with chimeric antigen receptors (CARs) demonstrated high therapeutic potential for targeting cancers of different origins. Beside CAR-T cells, natural killer (NK) cells represent promising alternative effectors that can be combined with CAR technology. Unlike T cells, primary NK cells and the NK cell line NK-92 can be applied as allogeneic off-the-shelf products with a reduced risk of toxicities.

ACCELERATE and European Medicines Agency Paediatric Strategy Forum for medicinal product development of checkpoint inhibitors for use in combination therapy in paediatric patients.

The third multistakeholder Paediatric Strategy Forum organised by ACCELERATE and the European Medicines Agency focused on immune checkpoint inhibitors for use in combination therapy in children and adolescents. As immune checkpoint inhibitors, both as monotherapy and in combinations have shown impressive success in some adult malignancies and early phase trials in children of single agent checkpoint inhibitors have now been completed, it seemed an appropriate time to consider opportunities for paediatric studies of checkpoint inhibitors used in combination. Among paediatric patients, early clinical studies of checkpoint inhibitors used as monotherapy have demonstrated a high rate of activity, including complete responses, in Hodgkin lymphoma and hypermutant paediatric tumours.

Treatment of children under 4 years of age with medulloblastoma and ependymoma in the HIT2000/HIT-REZ 2005 trials: Neuropsychological outcome 5 years after treatment.

Young children with brain tumours are at high risk of developing treatment-related sequelae. We aimed to assess neuropsychological outcomes 5 years after treatment. This cross-sectional study included children under 4 years of age with medulloblastoma (MB) or ependymoma (EP) enrolled in the German brain tumour trials HIT2000 and HIT-REZ2005.

Revisiting the genotype-phenotype correlation in children with medullary thyroid carcinoma: A report from the GPOH-MET registry.

Background: Medullary thyroid carcinomas (MTC) account for 3% to 5% of all thyroid cancers. In most cases, MTC is hereditary and occurs as part of the multiple endocrine neoplasia (MEN) type 2A and 2B syndromes. There is a strong genotype-phenotype correlation associated with the respective RET mutations, making risk-adapted management possible.

Efficacy and safety of D,L-3-hydroxybutyrate (D,L-3-HB) treatment in multiple acyl-CoA dehydrogenase deficiency.

Purpose: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a life-threatening, ultrarare inborn error of metabolism. Case reports described successful D,L-3-hydroxybutyrate (D,L-3-HB) treatment in severely affected MADD patients, but systematic data on efficacy and safety is lacking.

Methods: A systematic literature review and an international, retrospective cohort study on clinical presentation, D,L-3-HB treatment method, and outcome in MADD(-like) patients.

Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone.

Tumors of soft tissue and bone represent a heterogeneous group of neoplasias characterized by a wide variety of genetic aberrations. Albeit knowledge on tumorigenesis in mesenchymal tumors is continuously increasing, specific insights on altered signaling pathways as a basis for molecularly targeted therapeutic strategies are still sparse. The aim of this study was to determine the involvement of YAP1/TAZ-mediated signals in tumors of soft tissue and bone.

High failure rate 10.8 years after vastus medialis transfer and lateral release (Green's quadricepsplasty) for recurrent dislocation of the patella.

Purpose: In adolescent patients with recurrent patellar dislocation, the Green's quadricepsplasty stabilizes the patella in a combination of a lateral release, a transfer of the medial head of the quadriceps onto the lateral part of the patella and an imbrication of the medial patellar retinaculum and joint capsule. This study aimed to evaluate the long-term performance, considering re-dislocations and functional outcomes. We hypothesized a high failure rate in the long term.

Long-term surveillance of biologic therapies in systemic-onset juvenile idiopathic arthritis: data from the German BIKER registry.

Objective: Using data from the German Biologics JIA Registry (BIKER), long-term safety of biologics for systemic-onset JIA with regard to adverse events of special interest was assessed.

Methods: Safety assessments were based on adverse event reports after first dose through 90 days after last dose. Rates of adverse event, serious adverse event and 25 predefined adverse events of special interest were analysed.

Quality of survival assessment in European childhood brain tumour trials, for children below the age of 5 years.

The highest incidence rate of childhood brain tumours is in children below the age of five years, who are particularly vulnerable to the effects of treatments. The assessment of quality of survival (QoS) in multiple domains is essential to compare the outcomes for different tumour types and treatment regimens. The aim of this position statement is to present the domains of health and functioning to be assessed in children from birth to five years, to advance the collection of a common QoS data set in European brain tumour trials.

Desmoplastic myxoid tumor, SMARCB1-mutant: clinical, histopathological and molecular characterization of a pineal region tumor encountered in adolescents and adults.

Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly occurring in infants. Mutations of the SMARCB1 gene are the characteristic genetic lesion. SMARCB1-mutant tumors in adolescents and adults are rare and may show uncommon histopathological and clinical features.

Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective.

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports.

The challenges of influenza for public health.

Influenza, an infectious disease of the respiratory system, represents a major burden for public health. This disease affects all age groups with different prognosis, being life threatening for vulnerable individuals. Despite influenza being a vaccine-preventable disease, the control of the infection needs annual vaccination campaigns and constant improvements.

Neurological excitation in a 6-week-old male infant after morphine overdose.

While respiratory depression is a known complication of morphine overdose, the neuro-excitatory side effect of the morphine metabolite morphine-3-glucuronide is less widely known. Here, we report the case of an infant with neurological excitation after morphine overdose. The neuro-excitation in this infant was probably induced by an elevated morphine-3-glucuronide concentration.

Genotyping circulating tumor DNA of pediatric Hodgkin lymphoma.

We used hybrid capture-targeted next-generation sequencing of circulating cell-free DNA (ccfDNA) of pediatric Hodgkin lymphoma (PHL) patients to determine pathogenic mechanisms and assess the clinical utility of this method. Hodgkin-Reed/Sternberg (HRS) cell-derived single nucleotide variants, insertions/deletions, translocations and VH-DH-JH rearrangements were detected in pretherapy ccfDNA of 72 of 96 patients. Number of variants per patient ranged from 1 to 21 with allele frequencies from 0.

Treatment and outcome of patients with thoracic tumors of the Ewing sarcoma family: A report from the Cooperative Weichteilsarkom Studiengruppe CWS-81, -86, -91, -96, and -2002P trials.

Background: Ewing tumors are the most frequent malignant tumors of the chest wall in children and young adults. Surgical management of these tumors can be challenging. Optimal local control remains controversial.

Questionable Industry-Sponsored Postneonatal Pediatric Studies in Slovenia.

Background: US and EU pediatric laws promote industry-sponsored pediatric studies, based on the therapeutic orphans concept that claims discrimination of children in drug treatment and drug development.

Objective: We investigated the medical validity of international pediatric studies with centers in Slovenia, an EU member state, and challenge their medical utility.

Methods: We analyzed international industry-sponsored pediatric studies with centers in Slovenia, listed in www.