Neuroendocrine tumors (NETs) of the pancreas and midgut are extremely rare in children, and patients presenting with metastatic disease have poor survival. Given this rarity, treatments are extrapolated from guidelines for adults with NET. Recent clinical trials in adults with NETs have shown that the addition of peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE resulted in a disease control rate of nearly 80%, with minimal side effects. We report our experience using 177 Lu-DOTATATE to treat two pediatric patients with metastatic NET.There is limited information addressing the occurrence of esophageal strictures among the growing population of survivors of childhood cancer. Using the Childhood Cancer Survivor Study, we analyzed data from 17,121 5-year survivors and 3400 siblings to determine the prevalence and risk factors for esophageal strictures. Prevalence among survivors was 2.0% (95% confidence interval [CI] 1.8-2.2%), representing a 7.6-fold increased risk compared to siblings. Factors significantly associated with risk of esophageal stricture included diagnosis of Hodgkin lymphoma, greater chest radiation dose, younger age at cancer diagnosis, platinum chemotherapy, and hematopoietic stem cell transplantation. While uncommon, survivors are at risk for therapy-related esophageal strictures.Pediatric acute myeloid leukemia (AML) is a heterogeneous disease that requires a multifaceted treatment approach. Although outcomes for low-risk AML have improved significantly over recent decades, high-risk AML continues to be associated with an adverse prognosis. Recent advances in molecular diagnostics, risk stratification, and supportive care have contributed to improvements in outcomes in pediatric AML. Targeted approaches, for example, the use of tyrosine kinase inhibitors to treat FLT3-ITD AML, offer promise and are currently undergoing clinical investigation in pediatric patients. New approaches to hematopoietic stem cell transplantation, including the use of haploidentical donors, are significantly expanding donor options for patients with high-risk AML. This review provides an overview of recent advances in the treatment of pediatric AML that are likely to have clinical impact and reshape the standard of care.

Hearing impairment is associated with poor cognitive test performance in older adults. However, hearing’s impact on cognitive test completion is poorly described, and missing cognitive data due to hearing impairment could misestimate the association.

We investigated if hearing impairment is associated with missing neurocognitive scores in 3678 adults (72-94 years). Hearing impairment was defined by the better-ear pure tone average of speech-frequency thresholds (0.5-4kHz)>25 decibels.

Hearing impairment was associated with greater missingness on all auditory-only tests, including Logical Memory (prevalence ratio [PR] comparing ≥ moderate impairment vs normal hearing1.68, 95% confidence interval [CI] 1.26, 2.25) and Digits Backwards (PR 1.62; 95% CI 1.21, 2.17); and two non-auditory tests, Boston Naming (PR 1.61; 95% CI 1.21, 2.17) and Trail Making B (PR 1.55; 95% CI 1.29, 1.86). Models that imputed missing cognitive scores showed the strongest hearing-cognition associations.

Older adults with hearing impairment are less likely to complete cognitive testing, thereby underestimating the hearing impairment-cognition relationship.

Older adults with hearing impairment are less likely to complete cognitive testing, thereby underestimating the hearing impairment-cognition relationship.

Juvenile localized scleroderma (jLS) is an autoimmune disease of the skin in which the pathogenesis is not well understood due to its rarity. MK-4827 manufacturer Our goal was to determine the skin transcriptome of LS tissue compared with healthy controls to identify molecular targets using RNA sequencing (RNAseq). Differentially expressed genes (DEGs) identified in jLS patients were compared with histopathological features, clinical features and used to cluster jLS patients.

RNAseq was performed on paraffin-embedded skin (n=28 jLS, n=10 pediatric healthy) using the Illumina HTS and TrueSeq Access library preparation, aligned with STAR and analyzed using DESeq2. Standardized histology scoring was developed for inflammation and collagen deposition and was completed by 2 blinded pathologists. Spearman’s correlation was used to determine significance between DEGs and histology.

We identified 589 significant DEGs between jLS and controls. Hierarchical clustering demonstrated three distinct jLS immunophenotype groupings. Degree is-related pathways, and a third which corresponded to healthy skin gene expression. HLA Class II gene upregulation was observed within the inflammatory group, which has also been described for morphea peripheral blood and systemic sclerosis skin.There is growing recognition of the diversity of viruses that can infect the cells of the central nervous system (CNS). While the majority of CNS infections are successfully cleared by the immune response, some viral infections persist in the CNS. As opposed to resolved infections, persistent viruses can contribute to ongoing tissue damage and neuroinflammatory processes. In this manuscript, we provide an overview of the current understanding of factors that lead to viral persistence in the CNS including how viruses enter the brain, how these pathogens evade antiviral immune system responses, and how viruses survive and transmit within the CNS. Further, as the CNS may serve as a unique viral reservoir, we examine the ways in which persistent viruses in the CNS are being targeted therapeutically.Understanding excitation and inhibition balance in the brain begins with the tale of two basic types of neurons, glutamatergic projection neurons and GABAergic interneurons. The diversity of cortical interneurons is contributed by multiple origins in the ventral forebrain, various tangential migration routes, and complicated regulations of intrinsic factors, extrinsic signals, and activities. Abnormalities of interneuron development lead to dysfunction of interneurons and inhibitory circuits, which are highly associated with neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and intellectual disability. In this review, we mainly discuss recent findings on the development of cortical interneuron and on neurodevelopmental disorders related to interneuron dysfunction.