Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

Interferon-Alpha Administration Enhances CD8+ T Cell Activation in HIV Infection

Type I interferons play important roles in innate immune defense. In HIV infection, type I interferons may delay disease progression by inhibiting viral replication while at the same time accelerating disease progression by contributing to chronic immune activation.To investigate the effects of type I interferons in HIV-infection, we obtained cryopreserved peripheral blood mononuclear cell samples from 10 subjects who participated in AIDS Clinical Trials Group Study 5192, a trial investigating the activity of systemic administration of IFNα for twelve weeks to patients with untreated HIV infection. Using flow cytometry, we examined changes in cell cycle status and expression of activation antigens by circulating T cells and their maturation subsets before, during and after IFNα treatment.The proportion of CD38+HLA-DR+CD8+ T cells increased from a mean of 11.7% at baseline to 24.1% after twelve weeks of interferon treatment (p = 0.006). These frequencies dropped to an average of 20.1% six weeks after the end of treatment. In contrast to CD8+ T cells, the frequencies of activated CD4+ T cells did not change with administration of type I interferon (mean percentage of CD38+DR+ cells = 2.62% at baseline and 2.17% after 12 weeks of interferon therapy). As plasma HIV levels fell with interferon therapy, this was correlated with a "paradoxical" increase in CD8+ T cell activation (p<0.001).Administration of type I interferon increased expression of the activation markers CD38 and HLA DR on CD8+ T cells but not on CD4+ T cells of HIV+ persons. These observations suggest that type I interferons may contribute to the high levels of CD8+ T cell activation that occur during HIV infection

Development of Interlimb Movement Synchrony in the Rat Fetus

In the fetal rat, interlimb synchrony is a prominent form of temporally organized spontaneous motor activity in which movement of different limbs occurs at nearly the same instant. In the present study, synchrony profiles were created for different pairwise combinations of limbs over the last 5 days of gestation. Observed rates of synchrony differentiated from randomized time series from Gestational Day 19 to Day 21 (E19-E21), with forelimb synchrony emerging earlier than that of other limb pairs. Synchrony profiles were elevated at the shortest intervals between successive limb movements, indicating that movements became more tightly coupled toward the end of gestation. Interlimb synchrony appears to be a robust method of quantifying fetal movement and may prove useful as a tool for assessing prenatal nervous system functioning

Development of Interlimb Movement Synchrony in the Rat Fetus

In the fetal rat, interlimb synchrony is a prominent form of temporally organized spontaneous motor activity in which movement of different limbs occurs at nearly the same instant. In the present study, synchrony profiles were created for different pairwise combinations of limbs over the last 5 days of gestation. Observed rates of synchrony differentiated from randomized time series from Gestational Day 19 to Day 21 (E19-E21), with forelimb synchrony emerging earlier than that of other limb pairs. Synchrony profiles were elevated at the shortest intervals between successive limb movements, indicating that movements became more tightly coupled toward the end of gestation. Interlimb synchrony appears to be a robust method of quantifying fetal movement and may prove useful as a tool for assessing prenatal nervous system functioning

Development of Interlimb Movement Synchrony in Preterm Human Infants

Before birth, spontaneous movement occurs in all vertebrate species. Although these movements appear random, quantitative analysis has shown them to be organized in time and space. The temporal and spatial organization evident in fetal motor activity continues to be expressed by both animal and human infants after birth. Previous work in this lab has shown that quantification of spontaneous movement can reveal clear developmental patterns. One measure, interlimb synchrony, quantifies the temporal relationship of movements between pairwise limb combinations. In this study, spontaneous limb movement of preterm human infants born between 26–29 weeks post-conception was videotaped at weekly intervals in the Neonatal Intensive Care Unit (NICU) of the University of Iowa Hospitals and Clinics in collaboration with the Clinical Research Center (with Dr. Jack Widness, MD, and Karen Johnson, RN). Quantification of spontaneous movement in these infants revealed differences in the expression of interlimb synchrony across ages. In particular, interlimb synchrony appeared most pronounced at later ages (\u3e32 weeks), suggesting a developmental pattern in this form of motor organization. Supported by NIH grant RR00059 to the Clinical Research Center at the University of Iowa, and a UI Obermann Center for Advanced Studies Spelman Rockefeller Grant to SRR

Development of Interlimb Movement Synchrony in Preterm Human Infants

Before birth, spontaneous movement occurs in all vertebrate species. Although these movements appear random, quantitative analysis has shown them to be organized in time and space. The temporal and spatial organization evident in fetal motor activity continues to be expressed by both animal and human infants after birth. Previous work in this lab has shown that quantification of spontaneous movement can reveal clear developmental patterns. One measure, interlimb synchrony, quantifies the temporal relationship of movements between pairwise limb combinations. In this study, spontaneous limb movement of preterm human infants born between 26–29 weeks post-conception was videotaped at weekly intervals in the Neonatal Intensive Care Unit (NICU) of the University of Iowa Hospitals and Clinics in collaboration with the Clinical Research Center (with Dr. Jack Widness, MD, and Karen Johnson, RN). Quantification of spontaneous movement in these infants revealed differences in the expression of interlimb synchrony across ages. In particular, interlimb synchrony appeared most pronounced at later ages (\u3e32 weeks), suggesting a developmental pattern in this form of motor organization. Supported by NIH grant RR00059 to the Clinical Research Center at the University of Iowa, and a UI Obermann Center for Advanced Studies Spelman Rockefeller Grant to SRR