Subclonal TP53 and KRAS variants combined with poor treatment response identify ultra-high-risk pediatric T-ALL patients.

Variations in the TP53 and KRAS genes indicate a particularly adverse prognosis in relapsed pediatric T-ALL. We hypothesized that these variations might be subclonally present at disease onset and contribute to relapse risk. To test this, we examined two cohorts of children diagnosed with T-ALL: one with 81 patients who relapsed and 79 matched non-relapsing controls, and another with 226 consecutive patients, 30 of whom relapsed.

Effectiveness of structured, multidisciplinary long-term care for pediatric cancer survivors: protocol of the multicenter, randomized-controlled AELKI study.

Background: In Germany, around 2.250 children and adolescents are diagnosed with cancer each year. Despite generally positive long-term survival rates, many patients must cope with late effects of the disease and its treatment.

Stricture dilation balloon-assisted endoscopy in Crohn's disease: approach and intraprocedural outcomes with the single-balloon and double-balloon systems.

Background: Despite recent emerging literature involving the utility of endoscopic balloon dilation (EBD) of strictures balloon-assisted endoscopy (BAE), specifically regarding the management of Crohn's disease (CD), the optimal clinical approach with balloon systems has been largely neglected in academic literature.

Objectives: This study assesses the intra-procedural success and safety of EBD BAE for small bowel CD strictures while detailing our clinical approach and technique. Secondarily, we compare the single-balloon endoscope (SBE) and double-balloon endoscope (DBE) systems for EBD-related outcomes.

An early warning system for emerging SARS-CoV-2 variants.

Global sequencing and surveillance capacity for SARS-CoV-2 must be strengthened and combined with multidisciplinary studies of infectivity, virulence, and immune escape, in order to track the unpredictable evolution of the ongoing COVID-19 pandemic.

AMPLIFY-NEOVAC: a randomized, 3-arm multicenter phase I trial to assess safety, tolerability and immunogenicity of IDH1-vac combined with an immune checkpoint inhibitor targeting programmed death-ligand 1 in isocitrate dehydrogenase 1 mutant gliomas.

Introduction: Isocitrate dehydrogenase (IDH) mutations are disease-defining mutations in IDH-mutant astrocytomas and IDH-mutant and 1p/19q-codeleted oligodendrogliomas. In more than 80% of these tumors, point mutations in IDH type 1 (IDH1) lead to expression of the tumor-specific protein IDH1R132H. IDH1R132H harbors a major histocompatibility complex class II (MHCII)-restricted neoantigen that was safely and successfully targeted in a first-in human clinical phase 1 trial evaluating an IDH1R132H 20-mer peptide vaccine (IDH1-vac) in newly diagnosed astrocytomas concomitant to standard of care (SOC).

CD19 CAR T-cells for pediatric relapsed acute lymphoblastic leukemia with active CNS involvement: a retrospective international study.

Relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) may occur in the central nervous system (CNS). Most clinical trials of CAR T-cell therapy excluded patients with active CNS leukemia, partially for concerns of neurotoxicity. Here, we report an international study of fifty-five children and adolescents who received CAR T-cell therapy for relapsed BCP-ALL with CNS involvement at the time of referral.

A vaccine targeting mutant IDH1 in newly diagnosed glioma.

Mutated isocitrate dehydrogenase 1 (IDH1) defines a molecularly distinct subtype of diffuse glioma. The most common IDH1 mutation in gliomas affects codon 132 and encodes IDH1(R132H), which harbours a shared clonal neoepitope that is presented on major histocompatibility complex (MHC) class II. An IDH1(R132H)-specific peptide vaccine (IDH1-vac) induces specific therapeutic T helper cell responses that are effective against IDH1(R132H) tumours in syngeneic MHC-humanized mice.

Blinatumomab in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia.

Objective: Pediatric patients with relapsed or refractory acute lymphoblastic leukemia have a poor prognosis. We here assess the response rates, adverse events, and long-term follow-up of pediatric patients with relapsed/refractory acute lymphoblastic leukemia receiving blinatumomab.

Methods: Retrospective analysis of a single-center experience with blinatumomab in 38 patients over a period of 10 years.

A randomized, controlled, multi-center trial of the efficacy and safety of the Occlutech Figulla Flex-II Occluder compared to the Amplatzer Septal Occluder for transcatheter closure of secundum atrial septal defects.

Aims: The aim of this study was to compare the efficacy and safety of the Occlutech Figulla Flex II Occluder (OFFII) with the Amplatzer Septal Occluder (ASO) in patients > 8kg undergoing transcatheter ASD closure.

Methods And Results: Randomized, controlled, multi-center prospective clinical trial with randomization 2:1 in favor of the OFFII. Primary efficacy endpoint was the rate of successful device placement and defect closure without major complications at hospital discharge.

Outcomes of Pregnancies With Maternal/Paternal Exposure in the Tofacitinib Safety Databases for Ulcerative Colitis.

Background: Active inflammatory bowel disease increases the risk of adverse pregnancy outcomes. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). As a small molecule, tofacitinib is likely to cross the placental barrier; however, information on the effects of tofacitinib on pregnancy outcomes is limited.

Quality of Care in Ulcerative Colitis: A Modified Delphi Panel Approach.

Objectives: To establish clinical consensus on important and relevant quality-of-care (QoC) attributes in ulcerative colitis (UC) treatment that may improve treatment outcomes and guide best practices.

Methods: Thirty-eight QoC attributes were identified in a literature review. Sixteen European-based experts were selected based on their contributions to UC guidelines, publications, and patient care.

Granulocyte/monocyte adsorptive apheresis for the treatment of therapy-refractory chronic active ulcerative colitis.

Objectives: Current options for patients with steroid-dependent, chronic-active ulcerative colitis (UC) with insufficient response/intolerance to immunosuppressants (ISs) and/or biologics are limited. The aim of this study was to assess the long-term outcome of granulocyte/monocyte adsorptive (GMA) apheresis (Adacolumn) in this population.

Materials And Methods: Ninety five adults with steroid-dependent active UC and insufficient response/intolerance to IS and/or TNF inhibitors received 5-8 aphereses in a single induction series of ≤10 weeks.

Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000.

Induction therapy for childhood acute lymphoblastic leukemia (ALL) traditionally includes prednisone; yet, dexamethasone may have higher antileukemic potency, leading to fewer relapses and improved survival. After a 7-day prednisone prephase, 3720 patients enrolled on trial Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL 2000 were randomly selected to receive either dexamethasone (10 mg/m(2) per day) or prednisone (60 mg/m(2) per day) for 3 weeks plus tapering in induction. The 5-year cumulative incidence of relapse (± standard error) was 10.

Safety and Efficacy of Granulocyte/Monocyte Apheresis in Steroid-Dependent Active Ulcerative Colitis with Insufficient Response or Intolerance to Immunosuppressants and/or Biologics [the ART Trial]: 12-week Interim Results.

Background And Aims: Patients with active, steroid-dependent ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologic therapies have limited treatment options. Adacolumn, a granulocyte/monocyte adsorptive apheresis device, has shown clinical benefit in these patients. This study aimed to provide additional clinical data regarding the safety and efficacy of Adacolumn in this patient subgroup.

Features of cell death, mitochondrial activation and caspase dependence of rabbit anti-T-lymphocyte globulin signaling in lymphoblastic Jurkat cells are distinct from classical apoptosis signaling of CD95.

Rabbit anti-T-lymphocyte-globulin (ATG) is used for immunosuppression in organ and stem cell transplantation. The aim of this study was to investigate ATG-induced cell death compared to CD95-signaling of apoptosis. We measured features of cell death at the cell membrane, mitochondria, nuclei and caspase-3 cleavage.

Rabbit anti-T-lymphocyte globulin (ATG) persists with differential reactivity in patients' sera after full hematopoetic regeneration from allogeneic stem cell transplantation.

Background: Rabbit polyclonal anti-T-lymphocyte Globulin (ATG-F®, Fresenius) is widely used for GvHD prophylaxis in allogeneic stem cell transplantation (SCT). ATG has a wide epitope spectrum and has been shown to react with all compartments of peripheral blood mononuclear cells (PBMNCs). ATG induces apoptosis in all cellular compartments.

Attenuation of myocardial injury by HMGB1 blockade during ischemia/reperfusion is toll-like receptor 2-dependent.

Genetic or pharmacological ablation of toll-like receptor 2 (TLR2) protects against myocardial ischemia/reperfusion injury (MI/R). However, the endogenous ligand responsible for TLR2 activation has not yet been detected. The objective of this study was to identify HMGB1 as an activator of TLR2 signalling during MI/R.

Targeting leukocyte migration and adhesion in Crohn's disease and ulcerative colitis.

Crohn's disease and ulcerative colitis are two chronic inflammatory bowel diseases. Current biologic therapies are limited to blocking tumor necrosis factor alpha. However, some patients are primary non-responders, experience a loss of response, intolerance or side effects defining the urgent unmet need for novel treatments.

Endoscopic surveillance in Crohn's disease and ulcerative colitis: who needs what and when?

Crohn's disease and ulcerative colitis are chronic inflammatory diseases resulting from an inappropriate innate and adaptive immune response towards commensal microbiota. Patients with Crohn's disease and ulcerative colitis carry an increased risk of developing colon cancer and/or small bowel carcinoma, respectively. The colorectal cancer risks of ulcerative colitis and Crohn's disease with comparable surface area involvement and disease duration are very similar.

Monte Carlo simulation of contrast-enhanced whole brain radiotherapy on a CT scanner.

Purpose: To perform a feasibility study of contrast-enhanced whole brain radiotherapy for treating patients with multiple brain metastasis using a conventional computed tomography (CT) scanner.

Methods: The treatment dose was optimized to be applied in a single run using a maximum tube power of 5200 kWs at 140 kV. CT scans of a large and a small head were used as reference.

Anti-inflammatory effects of Saccharomyces boulardii mediated by myeloid dendritic cells from patients with Crohn's disease and ulcerative colitis.

Saccharomyces boulardii (Sb) is a probiotic yeast that has demonstrated efficacy in pilot studies in patients with inflammatory bowel disease (IBD). Microbial antigen handling by dendritic cells (DC) is believed to be of critical importance for immunity and tolerance in IBD. The aim was to characterize the effects of Sb on DC from IBD patients.

In vivo assessment of catheter positioning accuracy and prolonged irradiation time on liver tolerance dose after single-fraction 192Ir high-dose-rate brachytherapy.

Background: To assess brachytherapy catheter positioning accuracy and to evaluate the effects of prolonged irradiation time on the tolerance dose of normal liver parenchyma following single-fraction irradiation with 192Ir.

Materials And Methods: Fifty patients with 76 malignant liver tumors treated by computed tomography (CT)-guided high-dose-rate brachytherapy (HDR-BT) were included in the study. The prescribed radiation dose was delivered by 1 - 11 catheters with exposure times in the range of 844 - 4432 seconds.

Aberrant plasmacytoid dendritic cell distribution and function in patients with Crohn's disease and ulcerative colitis.

Dendritic cell (DC) function is believed to be of critical importance for the pathogenesis of inflammatory bowel disease (IBD). To date, most research in animal models and the few human data available is restricted to myeloid DC, while plasmacytoid DC (pDC) capable of controlling both innate and adaptive immune responses have not yet been investigated systematically in human Crohn's disease (CD) or ulcerative colitis (UC). CD11c(-) , CD303(+) /CD304(+) and CD123(+) pDC from peripheral blood (n = 90), mucosal tissue (n = 28) or mesenteric lymph nodes (n = 40) (MLNs) of patients with UC and CD or controls were purified and cultured.