Autoantibody status, neuroradiological and clinical findings in children with acute cerebellitis.

Background: Acute cerebellitis (AC) in children and adolescents is an inflammatory disease of the cerebellum due to viral or bacterial infections but also autoimmune-mediated processes.

Objective: To investigate the frequency of autoantibodies in serum and CSF as well as the neuroradiological features in children with AC.

Material And Methods: Children presenting with symptoms suggestive of AC defined as acute/subacute onset of cerebellar symptoms and MRI evidence of cerebellar inflammation or additional CSF pleocytosis, positive oligoclonal bands (OCBs), and/or presence of autoantibodies in case of negative cerebellar MRI.

Abnormal biomarkers predict complex FAS or FADD defects missed by exome sequencing.

Background: Elevated TCRαβCD4CD8 double-negative T cells (DNT) and serum biomarkers help identify FAS mutant patients with autoimmune lymphoproliferative syndrome (ALPS). However, in some patients with clinical features and biomarkers consistent with ALPS, germline or somatic FAS mutations cannot be identified on standard exon sequencing (ALPS-undetermined: ALPS-U).

Objective: We sought to explore whether complex genetic alterations in the FAS gene escaping standard sequencing or mutations in other FAS pathway-related genes could explain these cases.

Pilot study shows suppression of mineralocorticoid precursors under high-dose glucocorticoid therapy in pediatric acute lymphoblastic leukemia.

Glucocorticoids represent a key element in the treatment of pediatric acute lymphoblastic leukemia (ALL) and lead to adrenal suppression. We aimed to assess the differential response profile of adrenal steroids in children with ALL during BFM (Berlin-Frankfurt-Münster) induction treatment. Therefore, we performed liquid chromatography tandem-mass spectrometry (LC-MS/MS)-based steroid profiling of up to seven consecutive leftover morning serum samples derived from 11 patients (pts) with ALL before (day 0) and during induction therapy at days 1-5, 6-12, 13-26, 27-29, 30-35 and 36-40.

Clonal evolution in tyrosine kinase inhibitor-resistance: lessons from -models.

Introduction: Resistance in anti-cancer treatment is a result of clonal evolution and clonal selection. In chronic myeloid leukemia (CML), the hematopoietic neoplasm is predominantly caused by the formation of the BCR::ABL1 kinase. Evidently, treatment with tyrosine kinase inhibitors (TKIs) is tremendously successful.

Antimicrobial use in pediatric oncology and hematology in Germany and Austria, 2020/2021: a cross-sectional, multi-center point-prevalence study with a multi-step qualitative adjudication process.

Background: Due to the high risk of severe infection among pediatric hematology and oncology patients, antimicrobial use is particularly high. With our study, we quantitatively and qualitatively evaluated, based on institutional standards and national guidelines, antimicrobial usage by employing a point-prevalence survey with a multi-step, expert panel approach. We analyzed reasons for inappropriate antimicrobial usage.

Effect of two additional doses of intrathecal methotrexate during induction therapy on serious infectious toxicity in pediatric patients with acute lymphoblastic leukemia.

Although initial central nervous system (CNS) involvement is rarely detected in childhood acute lymphoblastic leukemia (ALL), risk-adapted CNS-directed therapy is essential for all patients. Treatment intensity depends on the initial CNS status. In the AIEOP-BFM ALL 2009 trial, patients with cytomorphologic detection of leukemic blasts in initial cerebrospinal fluid were classified as CNS2 or CNS3 and received five intrathecal doses of methotrexate (MTX) in induction therapy compared to patients with CNS1 status (no blasts detected) who received three doses.

Survey of young women's state of knowledge and perceptions about oral contraceptives in Germany.

Background: In Germany, we see a decline in the use of the oral contraceptive pill. Although there have been studies showing a lack of knowledge about the mode of action of the pill and alternative methods, the number of German women who feel well informed about the pill increased over recent years. At the same time, a trend to increasingly cover negative aspects of oral contraception has emerged in German journalism and social media.

Antimicrobial Use in Pediatric Oncology and Hematology: Protocol for a Multicenter Point-Prevalence Study With Qualitative Expert Panel Assessment.

Background: Because infections are a major driver of morbidity and mortality in children with hematologic or oncologic diseases, antimicrobials are frequently prescribed in pediatric oncology practice. However, excess or inappropriate use of antimicrobials is directly linked to the emergence of antimicrobial resistance. Although point-prevalence studies have examined the extent of antimicrobial use, a comprehensive qualitative evaluation of individual antimicrobial prescriptions remains lacking.

[Antibacterial Prophylaxis in Children and Adolescents Undergoing Therapy for Cancer - Statement of the Society of Pediatric Oncology and Hematology (GPOH) and of the German Society for Pediatric Infectious Diseases (DGPI) on Two Current International Guidelines].

Immunocompromised children and adolescents receiving treatment for cancer have an increased risk for potentially life-threatening infectious complications such as blood stream infections with Gram-positive and Gram-negative pathogens. Therefore, several centers for Pediatric Hematology and Oncology administer antibacterial prophylaxis to these patients to lower morbidity and mortality. Two pediatric specific guidelines on antibacterial prophylaxis were recently published.

[Recommendations for Diagnostics and Therapy of Children with Cancer Presenting with Fever and Neutropenia - Comparison of Two Current Guidelines].

Immunocompromised children and adolescents receiving treatment for cancer have a considerably increased risk for infection. Neutropenia is the most important single risk factor for infectious complications, and fever in neutropenia is considered as an emergency. Whereas guidelines for the management of fever in neutropenic adults have been established for decades, specific pediatric guidelines have not been developed until recently.

Neurotoxic side effects in children with refractory or relapsed T-cell malignancies treated with nelarabine based therapy.

The prognosis in children with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia (T-ALL) or lymphoblastic lymphoma (T-LBL) is poor. Nelarabine (Ara-G) has successfully been used as salvage therapy in these children, but has been associated with significant, even fatal, neurotoxicities. We retrospectively analysed 52 patients with r/r T-ALL/T-LBL aged ≤19 years who were treated with Ara-G alone (n = 25) or in combination with cyclophosphamide and etoposide (n = 27).

An Fc-engineered CD19 antibody eradicates MRD in patient-derived -rearranged acute lymphoblastic leukemia xenografts.

Antibody therapy constitutes a major advance in the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). To evaluate the efficacy and the mechanisms of action of CD19 monoclonal antibody therapy in pediatric BCP-ALL, we tested an Fc-engineered CD19 antibody carrying the S239D/I332E mutation for improved effector cell recruitment (CD19-DE). Patient-derived xenografts (PDX) of pediatric mixed-lineage leukemia gene ()-rearranged ALL were established in NOD.

The Cushion Method: A New Technique for the Recovery of Hydrophilic Nanocarriers.

Microencapsulation of hydrophilic therapeutic agents such as proteins or nucleotides into a nanocarrier is frequently accomplished in inverse (water-in-oil) emulsions. However, the redispersion of the nanocarriers in aqueous media often involves a complicated purification process, and the redispersion usually requires additional surfactants for its colloidal stability, which is not favored for biological applications. We propose a simple, fast, and mild method to recover hydrophilic nanocarriers prepared in inverse emulsions by temporary coating of the nanocarriers with biocompatible small molecules, so that the final aqueous dispersion of the nanocarriers can be dispersed with high recovery rate, minimal aggregation, and no additional surfactants.

Malignancy-associated haemophagocytic lymphohistiocytosis in children and adolescents.

Haemophagocytic lymphohistiocytosis (HLH) in the context of malignancy is mainly considered a challenge of adult haematology. While this association is also observed in children, little is known regarding inciting factors, appropriate treatment and prognosis. We retrospectively analysed 29 paediatric and adolescent patients for presenting features, type of neoplasm or preceding chemotherapy, treatment and outcome.

Secondary histiocytic sarcoma may cause apparent persistence or recurrence of minimal residual disease in childhood acute lymphoblastic leukemia.

Histiocytic sarcoma (HS) is a rare disease with poor prognosis which may develop subsequent to acute lymphoblastic leukemia (ALL). Here we report two children treated within the AIEOP-BFM ALL 2009 trial: one patient succumbed to fulminant hemophagocytic lymphohistiocytosis triggered by HS during ALL maintenance therapy, the other patient had a smoldering course of HS for over 2 years, and subsequently died after allogeneic stem cell transplantation. In both cases, HS and ALL were clonally related and apparent return of minimal residual disease (MRD) was detected by qPCR in bone marrow.

Cardiac anaplastic large cell lymphoma in an 8-year old boy.

We report on an 8 year old boy with primary cardiac anaplastic large cell lymphoma (ALCL), in whom the diagnosis was challenging and who was treated with modified chemotherapy without radiation therapy according to the ALCL 99 study protocol [1]. Two years and 4 months after completion of therapy the boy is in complete remission with normal cardiac function.

Clinical phenotype and functional analysis of a rare XIAP/BIRC4 mutation.

X-linked lymphoproliferative syndromes (XLP) are rare primary immunodeficiencies. Mutations within the XIAP/BIRC4 gene characterize XLP type 2 and cause XIAP deficiency. We present the case of a 5-year-old boy with a novel mutation of the XIAP/BIRC4 gene and describe the immunological phenotype for the first time.

RT-PCR assay for detection of Lassa virus and related Old World arenaviruses targeting the L gene.

This study describes an RT-PCR assay targeting the L RNA segment of arenaviruses. Conserved regions were identified in the polymerase domain of the L gene on the basis of published sequences for Lassa virus, lymphocytic choriomeningitis virus (LCMV), Pichinde virus and Tacaribe virus, as well as 15 novel sequences for Lassa virus, LCMV, Ippy virus, Mobala virus and Mopeia virus determined in this study. Using these regions as target sites, a PCR assay for detection of all known Old World arenaviruses was developed and optimized.

Renal complications associated with human parvovirus B19 infection in early childhood.

A previously healthy two-year-old girl presented with proteinuria and macroscopic haematuria. Laboratory findings included haemolytic anaemia with thrombocytopenia. Interestingly, continuing reticulocytopenia was noted.

Microstructural and tensile properties of elastin-based polypeptides crosslinked with genipin and pyrroloquinoline quinone.

Elastin is an elastomeric, self-assembling extracellular matrix protein with potential for use in biomaterials applications. Here, we compare the microstructural and tensile properties of the elastin-based recombinant polypeptide (EP) EP20-244 crosslinked with either genipin (GP) or pyrroloquinoline quinone (PQQ). Recombinant EP-based sheets were produced via coacervation and subsequent crosslinking.

Establishment of conventional and fluorescence resonance energy transfer-based real-time PCR assays for detection of pathogenic New World arenaviruses.

Background: Five of the known arenaviruses cause viral hemorrhagic fever in humans and are classified as biosafety level 4 pathogens. Four of the viruses, namely Junin, Guanarito, Machupo, and Sabia, belong to clade B of New World arenaviruses that also comprises the nonpathogenic viruses Tacaribe, Cupixi, and Amapari.

Objectives: To establish real-time reverse transcription (RT)-PCR assays for Junin and Guanarito virus based on fluorescence resonance energy transfer (FRET) probes, and a universal RT-PCR assay for all known clade B viruses with conventional read-out.