Speech in noise listening correlates identified in resting state and DTI MRI images.

This study presents an examination of the neural connectivity associated with processing speech in noisy environments, an ability that declines with age. We correlated subjects' speech-in-noise (SIN) ability with resting-state MRI scans and Fractional Anisotropy (FA) values from the auditory section of the corpus callosum, both with and without correcting for age. The results revealed that subjects who performed poorly on the right ear SIN test (QuickSIN, MedRx) had higher correlations between the primary auditory cortex and regions of the brain that process language.

Serum cytokine panels in pediatric clinical practice.

Background: Cytokines are soluble signaling proteins that regulate inflammation and coordinate immune responses. Serum cytokine panels are increasingly used in medical practice, yet our understanding of cytokines as biomarkers for disease remains limited.

Objective: We sought to analyze real-world single-center use of a multiplexed cytokine panel, correlate its results with diagnosis and severity, and explore its use in pediatric practice.

The role of donor type and pre-transplant immunosuppression on outcomes of hematopoietic stem cell transplantation in children and young adults with severe aplastic anemia.

Background: The goal of this study was to assess the effect of donor type and pre-transplant immunotherapy (IST) on outcomes of hematopoietic stem cell transplantation (HSCT) for children and young adults with severe aplastic anemia (SAA).

Methods: This retrospective, multi-center study included 52 SAA patients, treated in 5 pediatric transplant programs in Florida, who received HSCT between 2010 and 2020 as the first- or second-line treatment.

Results: The median age at HSCT for all 52 patients was 15 years (range 1-25).

INSPIRED Symposium Part 5: Expanding the Use of CAR T Cells in Children and Young Adults.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable efficacy in relapsed/refractory (r/r) B cell malignancies, including in pediatric patients with acute lymphoblastic leukemia (ALL). Expanding this success to other hematologic and solid malignancies is an area of active research and, although challenges remain, novel solutions have led to significant progress over the past decade. Ongoing clinical trials for CAR T cell therapy for T cell malignancies and acute myeloid leukemia (AML) have highlighted challenges, including antigen specificity with off-tumor toxicity and persistence concerns.

Clinical Trials on Cellular Therapy for Children and Adolescents With Cancer: A 15-Year Trend in the United States.

Introduction: Cellular therapies are frequently studied in clinical trials for pediatric patients with malignant disease. Characteristics of ongoing and completed cellular therapy clinical trials in the U.S.

Case Report: Insulin hypersensitivity in youth with type 1 diabetes.

Objective: Immediate type I, type III, and delayed type IV hypersensitivity reactions to insulin are rare, but potentially serious complications of exogenous insulin administration required for the treatment of type 1 diabetes (T1D).

Methods: We present four cases of insulin hypersensitivity reactions occurring in youth with T1D and a literature review of this topic.

Results: Insulin hypersensitivity reactions included types I, III, and IV with presentations ranging from localized urticaria, erythematous nodules, and eczematous plaques to anaphylaxis with respiratory distress.

INSPIRED Symposium Part 3: Prevention and Management of Pediatric Chimeric Antigen Receptor T Cell-Associated Emergent Toxicities.

Chimeric antigen receptor (CAR) T cell (CAR-T) therapy has emerged as a revolutionary cancer treatment modality, particularly in children and young adults with B cell malignancies. Through clinical trials and real-world experience, much has been learned about the unique toxicity profile of CAR-T therapy. The past decade brought advances in identifying risk factors for severe inflammatory toxicities, investigating preventive measures to mitigate these toxicities, and exploring novel strategies to manage refractory and newly described toxicities, infectious risks, and delayed effects, such as cytopenias.

Practice Preferences for Consolidative Hematopoietic Stem Cell Transplantation Following Tisagenlecleucel in Children and Young Adults with B Cell Acute Lymphoblastic Leukemia.

Treatment with tisagenlecleucel (tisa-cel) achieves excellent complete remission rates in children and young adults with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL), but approximately 50% maintain long-term remission. Consolidative hematopoietic stem cell transplantation (cHSCT) is a potential strategy to reduce relapse risk, but it carries substantial short- and long-term toxicities. Additionally, several strategies for management of B cell recovery (BCR) and next-generation sequencing (NGS) positivity post-tisa-cel exist, without an accepted standard.

Embryonic vitamin D deficiency programs hematopoietic stem cells to induce type 2 diabetes.

Environmental factors may alter the fetal genome to cause metabolic diseases. It is unknown whether embryonic immune cell programming impacts the risk of type 2 diabetes in later life. We demonstrate that transplantation of fetal hematopoietic stem cells (HSCs) made vitamin D deficient in utero induce diabetes in vitamin D-sufficient mice.

Peak Serum Cortisol Cutoffs to Diagnose Adrenal Insufficiency Across Different Cortisol Assays in Children.

Objective: Current peak serum cortisol cutoffs for the diagnosis of adrenal insufficiency (AI) after Cosyntropin stimulation have been established using polyclonal antibody (pAb) immunoassays. However, new and highly specific cortisol monoclonal antibody (mAb) immunoassays are being used more widely, which can potentially yield higher false positive rates. Thus, this study aimed to redefine the biochemical diagnostic cutoff points for AI in children when using a highly specific cortisol mAb immunoassay and liquid chromatography tandem mass spectrometry (LC/MS) to avoid unnecessary steroid use.

Steroid Use in the NICU: Treatment and Tapering.

The adrenal gland cortex produces life-sustaining steroid hormones that are critical for the development and survival of the fetus and neonate. Antenatal and postnatal administration of steroids has critical therapeutic effects in preterm infants. However, prolonged postnatal steroid therapy for more than 1 to 2 weeks is associated with iatrogenic adrenal insufficiency and should prompt consideration of a steroid taper and stress dose precautions.

HLH-like toxicities predict poor survival after the use of tisagenlecleucel in children and young adults with B-ALL.

Chimeric antigen receptor-associated hemophagocytic lymphohistiocytosis (HLH)-like toxicities (LTs) involving hyperferritinemia, multiorgan dysfunction, coagulopathy, and/or hemophagocytosis are described as occurring in a subset of patients with cytokine release syndrome (CRS). Case series report poor outcomes for those with B-cell acute lymphoblastic leukemia (B-ALL) who develop HLH-LTs, although larger outcomes analyses of children and young adults (CAYAs) with B-ALL who develop these toxicities after the administration of commercially available tisagenlecleucel are not described. Using a multi-institutional database of 185 CAYAs with B-ALL, we conducted a retrospective cohort study including groups that developed HLH-LTs, high-grade (HG) CRS without HLH-LTs, or no to low-grade (NLG) CRS without HLH-LTs.

SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report.

Background: Immunocompromised patients are at increased risk of SARS-CoV-2 infections. Patients undergoing chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-cell malignancies are uniquely immunosuppressed due to CAR T-mediated B-cell aplasia (BCA). While SARS-CoV-2 mortality rates of 33%-40% are reported in adult CAR T-cell recipients, outcomes in pediatric and young adult CAR T-cell recipients are limited.

The Influence of Motoric Maneuvers on Cervical Vestibular Evoked Myogenic Potentials (cVEMPs).

Background: The cervical vestibular evoked myogenic potential (cVEMP) is a vestibular response that is produced by the saccule in response to intense, often low-frequency, short-duration auditory stimuli, and is typically recorded from a contracted sternocleidomastoid (SCM) muscle. Previous research has shown that the amplitude of the cVEMP is related to the amount of SCM electromyographic (EMG) activity.

Purpose: The aim of this study was to determine the influence of various remote motoric maneuvers on the amplitude of the cVEMP, as well as whether they influence the level of SCM EMG activity.

tumors, but not tumor-derived cell lines, are adrenergic lineage, GD2+, and responsive to anti-GD2 antibody therapy.

Neuroblastoma is a commonly lethal solid tumor of childhood and intensive chemoradiotherapy treatment cures ~50% of children with high-risk disease. The addition of immunotherapy using dinutuximab, a monoclonal antibody directed against the GD2 disialoganglioside expressed on neuroblasts, improves survival when incorporated into front-line therapy and shows robust activity in regressing relapsed disease when combined with chemotherapy. Still, many children succumb to neuroblastoma progression despite receiving dinutuximab-based immunotherapy, and efforts to counteract the immune suppressive signals responsible are warranted.

Acute Left Ventricular Dysfunction Following Gemtuzumab Ozogamicin in Two Pediatric AML Patients.

Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-tumor antibiotic conjugate with proven efficacy in pediatric and adult patients with CD33+ acute myeloid leukemia. Adverse effects commonly associated with GO include hyperbilirubinemia, elevated transaminases, and sinusoidal obstruction syndrome. Cardiotoxicity has not been a commonly described adverse event.

Potential Role of IFNγ Inhibition in Refractory Cytokine Release Syndrome Associated with CAR T-cell Therapy.

Here we review the pathophysiology and management of cytokine release syndrome (CRS) secondary to immunotherapy, and potential options for CRS refractory to IL6 inhibition and glucocorticoids, for which there are no proven treatments. To illustrate, we describe a patient with B-cell acute lymphoblastic leukemia who developed refractory grade 4 CRS following CD19-directed chimeric antigen receptor T-cell therapy, treated with tocilizumab, methylprednisolone, siltuximab, and the IFNγ inhibitor emapalumab, with complete remission from leukemia for 12 months. See related article by Bailey et al.

Rates of adrenal insufficiency using a monoclonal vs. polyclonal cortisol assay.

Objectives: The diagnosis of adrenal insufficiency relies on clear cut-offs and accurate measurement of cortisol levels. Newer monoclonal antibody assays may increase the rate of diagnosis of adrenal insufficiency if traditional cortisol cut-off levels <18 mcg/dL (500 nmol/L) are applied. We aimed to determine if the rate of diagnosis of adrenal insufficiency using a 1 mcg Cosyntropin stimulation test varied with the change in cortisol assay from a polyclonal to a monoclonal antibody assay.

Proteomic Profiling of MIS-C Patients Reveals Heterogeneity Relating to Interferon Gamma Dysregulation and Vascular Endothelial Dysfunction.

Multi-system Inflammatory Syndrome in Children (MIS-C) is a major complication of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic in pediatric patients. Weeks after an often mild or asymptomatic initial infection with SARS-CoV-2 children may present with a severe shock-like picture and marked inflammation. Children with MIS-C present with varying degrees of cardiovascular and hyperinflammatory symptoms.