Clinical characteristics and outcome of central nervous system tumors harboring NTRK gene fusions.

Purpose: TRK fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients.

Experimental Design: We conducted an international retrospective cohort study of patients with TRK fusion-driven CNS tumors.

T-Cell Immunoglobulin and Mucin Domain 3 (TIM-3) Gene Expression as a Negative Biomarker of B-Cell Acute Lymphoblastic Leukemia.

B-cell acute lymphoblastic leukemia (B-ALL) accounts for 85% of all childhood ALL. Malignancies exhaust T and B cells, resulting in an increased expression of immune checkpoint receptors (ICRs), such as T-cell immunoglobulin and mucin domain 3 (TIM-3). TIM-3 has been found to be dysregulated in different types of cancer.

Herpesvirus Entry Mediator as an Immune Checkpoint Target and a Potential Prognostic Biomarker in Myeloid and Lymphoid Leukemia.

Herpesvirus entry mediator (HVEM) is a molecular switch that can modulate immune responses against cancer. The significance of HVEM as an immune checkpoint target and a potential prognostic biomarker in malignancies is still controversial. This study aims to determine whether HVEM is an immune checkpoint target with inhibitory effects on anti-tumor CD4 T cell responses in vitro and whether gene expression is dysregulated in patients with acute lymphocytic leukemia (ALL).

The Clinical Utility of a Tiered Approach to Pediatric Glioma Molecular Characterization for Resource-Limited Settings.

Purpose: Molecular characterization is key to optimally diagnose and manage cancer. The complexity and cost of routine genomic analysis have unfortunately limited its use and denied many patients access to precision medicine. A possible solution is to rationalize use-creating a tiered approach to testing which uses inexpensive techniques for most patients and limits expensive testing to patients with the highest needs.

Performance of the eHealth decision support tool, MIPOGG, for recognising children with Li-Fraumeni, DICER1, Constitutional mismatch repair deficiency and Gorlin syndromes.

Background: Cancer predisposition syndromes (CPSs) are responsible for at least 10% of cancer diagnoses in children and adolescents, most of which are not clinically recognised prior to cancer diagnosis. A variety of clinical screening guidelines are used in healthcare settings to help clinicians detect patients who have a higher likelihood of having a CPS. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) is an electronic health decision support tool that uses algorithms to help clinicians determine if a child/adolescent diagnosed with cancer should be referred to genetics for a CPS evaluation.

The clinical utility of integrative genomics in childhood cancer extends beyond targetable mutations.

We conducted integrative somatic-germline analyses by deeply sequencing 864 cancer-associated genes, complete genomes and transcriptomes for 300 mostly previously treated children and adolescents/young adults with cancer of poor prognosis or with rare tumors enrolled in the SickKids Cancer Sequencing (KiCS) program. Clinically actionable variants were identified in 56% of patients. Improved diagnostic accuracy led to modified management in a subset.

Congenital midline spinal hamartoma in an infant with DICER1 syndrome: A case report.

Congenital spinal hamartomas are rare benign tumors. They are mostly seen in infants and are typically asymptomatic at presentation. Spinal hamartomas have not been associated with any known cancer predisposition syndrome.

Malignant Melanotic Nerve Sheath Tumors: A Review of Clinicopathologic and Molecular Characteristics.

Malignant melanotic nerve sheath tumor (MMNST) which was formerly known as melanocytic schwannoma, is an uncommon aggressive type of nerve sheath tumor. It originates from nerve roots with clonal Schwann cell proliferation and melanin pigment production. MMNST which was once thought to be a benign tumor is now considered a malignant disease based on the latest 2020 World Health Organization classification of soft tissue tumors.

Acquired thrombotic thrombocytopenic purpura with isolated CFHR3/1 deletion-rapid remission following complement blockade.

Background: Thrombotic thrombocytopenic purpura (TTP) is caused by the abundance of uncleaved ultralarge von Willebrand factor multimers (ULvWF) due to acquired (autoantibody-mediated) or congenital vWF protease ADAMTS13 deficiency. Current treatment recommendations include plasma exchange therapy and immunosuppression for the acquired form and (fresh) frozen plasma for congenital TTP.

Case-diagnosis/treatment: A previously healthy, 3-year-old boy presented with acute microangiopathic hemolytic anemia, thrombocytopenia, erythrocyturia and mild proteinuria, but normal renal function, and elevated circulating sC5b-9 levels indicating complement activation.

Success importance and urge magnitude as determinants of cardiovascular response to a behavioral restraint challenge.

Decades of research have investigated a conceptual analysis concerned with determinants and cardiovascular correlates of effort in people confronted with performance challenges, that is, opportunities to alter some course of events by acting. One suggestion is that effort and associated cardiovascular responses should be determined jointly by the difficulty of meeting a challenge and the importance of doing so. The present experiment tested this in a context involving behavioral restraint, that is, effortful resistance against a behavioral impulse or urge.