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STAT3, IL-6 and inflammatory response pathway signaling associated gene expression is upregulated in Group A EPN.

PDF file 98K, Microscopy data with representative photos and quantification

Experimentally determined STAT3 upregulated genes.

PDF file 31K, Autophagic flux by flow cytometry in vemurafenib treated cells

Ependymoma (EPN) in childhood is a brain tumor with substantial mortality. Inflammatory response has been identified as a molecular signature of high-risk Group A EPN. To better understand the biology of this phenotype and aid therapeutic development, transcriptomic data from Group A and B EPN patient tumor samples, and additional malignant and normal brain data, were analyzed to identify the mechanism underlying EPN Group A inflammation. Enrichment of IL6 and STAT3 pathway genes were found to distinguish Group A EPN from Group B EPN and other brain tumors, implicating an IL6 activation of STAT3 mechanism. EPN tumor cell growth was shown to be dependent on STAT3 activity, as demonstrated using shRNA knockdown and pharmacologic inhibition of STAT3 that blocked proliferation and induced apoptosis. The inflammatory factors secreted by EPN tumor cells were shown to reprogram myeloid cells, and this paracrine effect was characterized by a significant increase in pSTAT3 and IL8 secretion. Myeloid polarization was shown to be dependent on tumor secretion of IL6, and these effects could be reversed using IL6-neutralizing antibody or IL6 receptor–targeted therapeutic antibody tocilizumab. Polarized myeloid cell production of IL8 drove unpolarized myeloid cells to upregulate CD163 and to produce a number of proinflammatory cytokines. Collectively, these findings indicate that constitutive IL6/STAT3 pathway activation is important in driving tumor growth and inflammatory cross-talk with myeloid cells within the Group A EPN microenvironment. Effective design of Group A–targeted therapy for children with EPN may require reversal of this potentially immunosuppressive and protumor pathway. Cancer Immunol Res; 3(10); 1165–74. ©2015 AACR.

FDA panel: Details of drug screen library of 97 FDA approved anticancer active compounds. FDA drug targets: Genes corresponding to known protein targets of compounds in FDA approved oncology drug screen library, corresponding Affymetrix probeset IDs and literature source. GSEA of axitinib Tx: Axitinib-induced enrichment and depletion of MSigDB "Hallmark" genesets in transcriptomic profiles of axitinib-treated versus untreated controls.

IL-6 is the driving cytokine for immune suppressive phenotype observed in 811 CM monocytes.

S3I-201 effects on cell cycle EPN cell line 811 and apoptosis in EPN cell line 723.

PDF file 186K, Figures legends for supplementary data figures

Children with ependymoma (EPN) are cured in less than 50% of cases, with little improvement in outcome over the last several decades. Chemotherapy has not affected survival in EPN, due in part to a lack of preclinical models that has precluded comprehensive drug testing. We recently developed two human EPN cell lines harboring high-risk phenotypes which provided us with an opportunity to execute translational studies. EPN and other pediatric brain tumor cell lines were subject to a large-scale comparative drug screen of FDA-approved oncology drugs for rapid clinical application. The results of this in vitro study were combined with in silico prediction of drug sensitivity to identify EPN-selective compounds, which were validated by dose curve and time course modeling. Mechanisms of EPN-selective antitumor effect were further investigated using transcriptome and proteome analyses. We identified three classes of oncology drugs that showed EPN-selective antitumor effect, namely, (i) fluorinated pyrimidines (5-fluorouracil, carmofur, and floxuridine), (ii) retinoids (bexarotene, tretinoin and isotretinoin), and (iii) a subset of small-molecule multireceptor tyrosine kinase inhibitors (axitinib, imatinib, and pazopanib). Axitinib's antitumor mechanism in EPN cell lines involved inhibition of PDGFRα and PDGFRβ and was associated with reduced mitosis-related gene expression and cellular senescence. The clinically available, EPN-selective oncology drugs identified by our study have the potential to critically inform design of upcoming clinical studies in EPN, in particular for those children with recurrent EPN who are in the greatest need of novel therapeutic approaches. Mol Cancer Ther; 17(9); 1984–94. ©2018 AACR.

PDF file 121K, Incucyte growth analysis and western blot analysis

Apoptosis time courses for EPN cell lines 811 and 928 treated with floxuridine, bexarotene, and axitinib all at 1µM, as measured by live cell imaging (IncuCyte) ofcaspase 3/7 activation (green objects/mm2). Idarubicin (1µM) provides a positive control for apoptosis and untreated cells serve as a negative control.

Ratio of Group A EPN IL6/STAT3 pathway genes in tumor versus the myeloid compartments.

Consensus NMF of 81 primary ependymoma samples at k = 3 delineates two posterior fossa subgroups in the study cohort.

Supplemental Figure Legends

PDF file 2464K, Timeline of treatments and clinical responses

PDF file 117K,Propidium idodide results and western blot analysis

PDF file 17K, Growth curve with vemurafenib treatments

Expression of EPN-selective drug targets in primary PFA patient samples versus cerebellum. Gene expression for (A) RARB, (B) PDGFRB, (C) VEGFR2 (KDR) and (D) VEGFC in twelve PFA patient samples and 4 pediatric cerebellum samples. Red bars represent mean and standard deviation. P-values = student's t-test.

Astrocytomas account for the majority of malignant brain tumors diagnosed in both adult and pediatric patients. The therapies available to treat these neoplasms are limited, and the prognosis associated with high-grade lesions is extremely poor. Mer (MerTK) and Axl receptor tyrosine kinases (RTK) are expressed at abnormally high levels in a variety of malignancies, and these receptors are known to activate strong antiapoptotic signaling pathways that promote oncogenesis. In this study, we found that Mer and Axl mRNA transcript and protein expression were elevated in astrocytic patient samples and cell lines. shRNA-mediated knockdown of Mer and Axl RTK expression led to an increase in apoptosis in astrocytoma cells. Apoptotic signaling pathways including Akt and extracellular signal–regulated kinase 1/2, which have been shown to be activated in resistant astrocytomas, were downregulated with Mer and Axl inhibition whereas poly(ADP-ribose) polymerase cleavage was increased. Furthermore, Mer and Axl shRNA knockdown led to a profound decrease of astrocytoma cell proliferation in soft agar and a significant increase in chemosensitivity in response to temozolomide, carboplatin, and vincristine treatment. Our results suggest Mer and Axl RTK inhibition as a novel method to improve apoptotic response and chemosensitivity in astrocytoma and provide support for these oncogenes as attractive biological targets for astrocytoma drug development. Mol Cancer Ther; 9(5); 1298–307. ©2010 AACR.

PDF file - 1806K, Supplementary Figure S1. Hierarchical clustering of breast cancer cell lines transduced with an autophagy-focused shRNA library produced two main clusters. Supplementary Figure S2. ATG5, ATG7 and BECN1 shRNAs decreased protein levels in all cell lines tested. Supplementary Figure S3. Autophagy inhibition induces cell death in some cell lines but not others. MCF7, MDAMB231 and MDAMB468 cells were transduced with a lentivirus expressing shRNAs against ATG7 or BECN1, plated and evaluated for cell death with propidium iodide (red) staining after 48 h. Supplementary Figure S4. Triple negative cell lines have constitutively activated JAK/STAT pathway and autophagy regulates their STAT3 phosphorylation status.

MOV file - 3729K, MDAMB231 cells were transduced with a Non-silencing shRNA and imaged for 48h.

MOV file - 3141K, MCF7 cells were transduced with a Non-silencing shRNA and imaged for 48h.

PDF file - 117K, Supplementary table 1. Changes in shRNAs included in the autophagy library per cell line. Cells were transduced with a shRNA library containing autophagy-focused shRNAs. After transduction, the first sample (Post-transduction, PT) was collected. Growth sample (G) was collected after 15 days in culture. Both samples were done in quintuplicate. Table shows comparison of PT versus G samples. shRNAs were considered to be up (Sign Tag = U), or down-regulated (Sign Tag = D) in the growth sample when ANOVA p-value < 0.05 and fold change absolute value > 2.

MOV file - 2644K, MDAMB231 cells were transduced with an ATG7 shRNA and imaged for 48h.

MOV file - 2592K, MDAMB468 cells were transduced with an ATG7 shRNA and imaged for 48h.

MOV file - 2566K, MCF7 cells were transduced with an ATG7 shRNA and imaged for 48h.

Louisiana rice is attacked by a complex of lepidopteran stem borers that injure the vegetative and reproductive stages of rice, reducing tillering and grain output. Currently, insecticidal seed treatments are used in Louisiana as a preemptive means to control stem borers in rice. Our objective was to better understand the spatial distribution of stem borers in Louisiana rice fields. Thirteen nontreated commercial rice fields in Louisiana were mapped using GPS software and surveyed for stem borer damage in 2017 and 2018. Damage was recorded by counting the number of blank panicles (whiteheads) within quadrats located at different areas in each field. An ANOVA, spatial interpolation, hotspot analysis, and negative binomial regression were used to determine where stem borer injury was concentrated and whether the distribution of these pests was influenced by rice stand count, field composition, and site location. The results show that stem borers are typically aggregated along field edges, with population density decreasing toward the center of rice fields. Stem borer damage was 4.2- and 3.9-fold greater along field edges than in field centers in 2017 and 2018, respectively. Hotspot spatial analysis revealed 41.7 and 52.1% of low-density clusters occurred at or near field centers, respectively. Negative binomial regression revealed stem borer injury declines with increasing distance from field edges, with regional differences in infestation levels. This suggests stem borer control efforts could be spatially targeted to improve the efficiency of pest management.

Brain tumors are the most common solid tumor in children, and low-grade gliomas (LGGs) are the most common childhood brain tumor. Here, we report on 3 patients with LGG harboring previously unreported or rarely reported RAF fusions: FYCO1-RAF1, CTTNBP2-BRAF, and SLC44A1-BRAF. We hypothesized that these tumors would show molecular similarity to the canonical KIAA1549-BRAF fusion that is the most widely seen alteration in pilocytic astrocytoma (PA), the most common pediatric LGG variant, and that this similarity would include mitogen-activated protein kinase (MAPK) pathway activation. To test our hypothesis, we utilized immunofluorescent imaging and RNA-sequencing in normal brain, KIAA1549-BRAF-harboring tumors, and our 3 tumors with novel fusions. We performed immunofluorescent staining of ERK and phosphorylated ERK (p-ERK), identifying increased p-ERK expression in KIAA1549-BRAF fused PA and the novel fusion samples, indicative of MAPK pathway activation. Geneset enrichment analysis further confirmed upregulated downstream MAPK activation. These results suggest that MAPK activation is the oncogenic mechanism in noncanonical RAF fusion-driven LGG. Similarity in the oncogenic mechanism suggests that LGGs with noncanonical RAF fusions are likely to respond to MEK inhibitors.

Rice water weevil, Lissorhoptrus oryzophilus Kuschel (Coleoptera: Curculionidae), is a destructive insect pest of rice in the United States. The pruning of rice roots by L. oryzophilus larvae can cause up to 25% yield loss. Currently, insecticidal seed treatments are used in the Louisiana rice industry as a pre-emptive means of controlling this weevil species. Our objective was to gain a better understanding of the spatial distribution of L. oryzophilus in Louisiana rice fields. Thirteen untreated commercial rice fields in Louisiana were mapped using GPS software, and surveyed for L. oryzophilus larvae over two years (2017 and 2018). An ANOVA, spatial interpolation, hotspot analysis, and multiple linear regression were used to determine where populations of L. oryzophilus were concentrated and whether distributions of the pest were related to edge effects. The results showed that L. oryzophilus larvae are typically aggregated along the edges of rice fields, with populations decreasing toward the center of rice fields. Lissorhoptrus oryzophilus densities were 3.3- and 2.2- fold greater along field edges than in field centers in 2017 and 2018, respectively. Hotspot spatial analysis revealed 59% and 32% of low-density clusters occurred at or near field centers, respectively. Multiple linear regression revealed larval densities decline with increasing distance from overwintering sites and alternative habitats (such as tree lines and levees containing bunch grasses and other alternative noncrop plants). These results suggest potential for insecticidal seed treatments to be applied selectively within rice fields to control this pest.

Registered nurses (RNs) are national assets who provide quality patient care, especially during the corona virus disease 2019 pandemic. Currently, healthcare organizations are overwhelmed with ill patients who require RNs with specialty experiences. Curtailment and cancellation by healthcare organizations of civilian and military transition-to-practice programs for newly licensed RNs are at risk. If this phenomenon continues, current and future nursing shortages will prevail.

Optic pathway glioma (OPG) comprises 10% of pediatric brain tumors and 40% of all pediatric low-grade gliomas (pLGGs). While generally considered benign pathologically, many require interventions with chemotherapy, radiation, or targeted therapies. Management has historically foregone tissue diagnosis given the classical clinical/radiographic presentation of these tumors, inability to safely remove the lesions surgically, and efficacy and safety of available chemotherapy options. Furthermore, when considering such aspects as their delicate location, the role of surgery continues to be heavily debated. More recently, however, a greater understanding of the genetic drivers of OPGs has made operative tissue sampling a critical step in management planning, specifically for patients without Neurofibromatosis, Type I (NF1). Given the need for long-term, complex management of pediatric OPGs, it is crucial that a multidisciplinary approach is employed, and the rapidly expanding role of molecular characterization be incorporated into their management.

The sugarcane aphid, Melanaphis sacchari Zehntner, is an economically damaging pest of sorghum, Sorghum bicolor (L.), across the southern United States. Field experiments investigated impacts of sorghum cultivar, nitrogen fertilization, and insecticides on M. sacchari infestations and sorghum yields in Louisiana and South Carolina in 2017 and 2018. In South Carolina, M. sacchari densities in unprotected plots peaked on 30–31 July of both years before declining by early- to mid-August. In Louisiana, infestations peaked on 26 and 12 July for 2017 and 2018, respectively, and declined by mid-August. Nitrogen fertilization influenced M. sacchari densities in Louisiana in 2018 with the highest-level infestations recorded from plots that received high N rates. Densities of M. sacchari on susceptible sorghum cultivar, DKS 38-88, were 1.5- to 2.3-fold greater than on DKS 37-07 in both years in Louisiana and in 2018 in South Carolina. Nitrogen fertilization was associated with improved sorghum yields in Louisiana experiments. Sorghum yields across experiments were 2- to 4-fold greater in plots protected with multiple insecticide applications than in unprotected plots. Yield from plots with insecticides sprayed once at currently used action thresholds differed from unprotected plots only in the 2018 Louisiana experiment. Results from these experiments indicate insecticidal protection of susceptible sorghum cultivars remains critical throughout much of the southern United States. Further research is needed to develop integrated management programs that incorporate fertilization manipulation, cultivar resistance, and insecticidal control.

Bio-nanotechnology offers eco-friendly processes for the synthesis of stable nanoparticles (NPs). We hypothesized that microorganisms isolated from the root nodules of leguminous plants would biosynthesize silver (Ag) bio-nanoparticles. Clover root nodules enriched with nutrient broth (NB) produced four distinct colonies on NA plates. Microbial colonies were purified by repeated streaking and designated as SS6, SS7, SS8, and SS9 for identification using 16S rRNA sequencing. Four species of Pseudomonas were identified with a similarity score of over 99% using the EZ Taxon search engine, and tested for extracellular biosynthesis of AgNPs. Microorganism Pseudomonas taiwanensis-SS8 with alkaliphilic growth characteristics reduced the AgNO3 solution into AgNPs in the shortest time period. AgNPs were characterized using UV-Vis spectrophotometry and electron and transmission electron microscopy. A number of physical (i.e., temperature and time) and chemical (i.e., pH and growth media) parameters were optimized. An efficient polydispersal biosynthesis of AgNPs at pH 8–9 after 48 hrs in NB growth medium was observed. In addition, the AgNPs showed antimicrobial properties against 16 commonly occurring pathogenic microorganisms.

Hutton (discovered in 1973) and NW Hutton (discovered in 1975), together with Q-West (discovered in 1994) and Darwin (discovered in 1983, undeveloped), are part of a single petroleum system. The main fields were defined as two separate legal entities. Although Q–West covered multiple blocks, it was wholly developed via the Hutton platform. Together, Hutton and NW Hutton produced 328 MMbbl of oil and a small quantity of associated gas from Middle Jurassic Brent Group sandstones. The trap is a complex series of tilted fault blocks sealed by Mid–Upper Jurassic Heather and Kimmeridge Clay Formation mudstones. Oil was sourced from the Kimmeridge Clay Formation, which is mature for oil generation in the hanging walls to the field-bounding faults and deep on the footwall flanks. NW Hutton underperformed relative to Hutton. In part this was due to the poorer reservoir quality encountered at depth compared with the shallower Hutton Field but a significant component of the underperformance was due to the way in which the field was developed and then operated. Both fields contain areas of unproduced and unswept oil, with the NW Hutton portion having the largest remaining oil in place.

The cohort included all patients treated with high-dose chemotherapy and autologous stem cell transplant for primary brain tumors at our institution from 2011 to 2017. Rates of local control, progression-free survival, overall survival, and radiation-associated injury were assessed.Of the 37 eligible patients, 29 (78%) received peri-transplant RT. Patients treated with RT were more likely to have metastatic (Peri-transplant RT was used for high-risk disease. Oncologic outcomes after RT were encouraging. However, 2 cases of grade 5 myelopathy were observed. If used cautiously, RT may contribute to durable remission in patients at high risk of relapse.

Hymenoptera venom allergy is characterised by systemic anaphylactic reactions that occur in response to stings from members of the Hymenoptera order. Stinging by social Hymenoptera such as ants, honeybees, and vespids is one of the 3 major causes of anaphylaxis; along with food and drug exposure, it accounts for up to 43% of anaphylaxis cases and 20% of anaphylaxis-related fatalities. Despite their recognition as being of considerable public health significance, stinging ant venoms are relatively unexplored in comparison to other animal venoms and may be overlooked as a cause of venom allergy. Indeed, the venoms of stinging ants may be the most common cause of anaphylaxis in ant endemic areas. A better understanding of the natural history of venom allergy caused by stinging ants, their venom components, and the management of ant venom allergy is therefore required. This article provides a global view on allergic reactions to the venoms of stinging ants and the contemporary approach to diagnose and manage ant venom allergy. Refereed/Peer-reviewed

High-grade gliomas (HGG) afflict both children and adults and respond poorly to current therapies. Epigenetic regulators have a role in gliomagenesis, but a broad, functional investigation of the impact and role of specific epigenetic targets has not been undertaken. Using a two-step, in vitro/in vivo epigenomic shRNA inhibition screen, we determine the chromatin remodeler BPTF to be a key regulator of adult HGG growth. We then demonstrate that BPTF knockdown decreases HGG growth in multiple pediatric HGG models as well. BPTF appears to regulate tumor growth through cell self-renewal maintenance, and BPTF knockdown leads these glial tumors toward more neuronal characteristics. BPTF’s impact on growth is mediated through positive effects on expression of MYC and MYC pathway targets. HDAC inhibitors synergize with BPTF knockdown against HGG growth. BPTF inhibition is a promising strategy to combat HGG through epigenetic regulation of the MYC oncogenic pathway.

Autophagy allows for cellular material to be delivered to lysosomes for degradation resulting in basal or stress-induced turnover of cell components that provide energy and macromolecular precursors. These activities are thought to be particularly important in cancer where both tumor-promoting and tumor-inhibiting functions of autophagy have been described. Autophagy has also been intricately linked to apoptosis and programmed cell death, and understanding these interactions is becoming increasingly important in improving cancer therapy and patient outcomes. In this review, we consider how recent discoveries about how autophagy manipulation elicits its effects on cancer cell behavior can be leveraged to improve therapeutic responses.

Rare Brain Tumor Registry., [Background] Embryonal tumours with multi-layered rosettes (ETMRs) are a newly recognised, rare paediatric brain tumour with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and scarce clinical data, disease features and determinants of outcomes for these tumours are poorly defined. We did an integrated clinicopathological and molecular analysis of primary ETMRs to define clinical phenotypes, and to identify prognostic factors of survival and key treatment modalities for this orphan disease., [Methods] Paediatric patients with primary ETMRs and tissue available for analyses were identified from the Rare Brain Tumor Consortium global registry. The institutional histopathological diagnoses were centrally re-reviewed as per the current WHO CNS tumour guidelines, using histopathological and molecular assays. Only patients with complete clinical, treatment, and survival data on Nov 30, 2019, were included in clinicopathological analyses. Among patients who received primary multi-modal curative regimens, event-free survival and overall survival were determined using Cox proportional hazard and log-rank analyses. Univariate and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) with 95% CIs for clinical, molecular, or treatment-related prognostic factors., [Findings] 159 patients had a confirmed molecular diagnosis of primary ETMRs (median age at diagnosis 26 months, IQR 18–36) and were included in our clinicopathological analysis. ETMRs were predominantly non-metastatic (94 [73%] of 128 patients), arising from multiple sites; 84 (55%) of 154 were cerebral tumours and 70 (45%) of 154 arose at sites characteristic of other brain tumours. Hallmark C19MC alterations were seen in 144 (91%) of 159 patients; 15 (9%) were ETMR not otherwise specified. In patients treated with curative intent, event-free survival was 57% (95% CI 47–68) at 6 months and 31% (21–42) at 2 years; overall survival was 29% (20–38) at 2 years and 27% (18–37) at 4 years. Overall survival was associated with non-metastatic disease (HR 0·48, 95% CI 0·28–0·80; p=0·0057) and non-brainstem location (0·42 [0·22–0·81]; p=0·013) on univariate analysis, as well as with gross total resection (0·30, 0·16–0·58; p=0·0014), high-dose chemotherapy (0·35, 0·19–0·67; p=0·0020), and radiotherapy (0·21, 0·10–0·41; p, [Interpretation] Prompt molecular diagnosis and post-surgical treatment with intensive multi-modal therapy tailored to patient-specific risk features could improve ETMR survival., Canadian Institute of Health Research, Canada Research Chair Awards, Australian Lions Childhood Cancer Research Foundation, Spanish Society of Pediatrics, Consejería de Salud y Familias de la Junta de Andalucía, Miracle Marnie, Phoebe Rose Rocks, Tali's Funds, Garron Cancer Centre, Grace's Walk, Meagan's Hug, Brainchild, Nelina's Hope, and Jean Martel Foundation.

Objectives We evaluated the length of time immunocompromised children (ICC) remain positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), identified factors associated with viral persistence, and determined cycle threshold (C T) values of children with viral persistence as a surrogate of viral load. Methods We conducted a retrospective cohort study of ICC at a pediatric hospital from March 2020 to March 2021. Immunocompromised status was defined as primary, secondary, or acquired due to medical comorbidities/immunosuppressive treatment. The primary outcome was time to first of two consecutive negative SARS‐CoV‐2 polymerase chain reaction (PCR) tests at least 24 hours apart. Testing of sequential clinical specimens from the same subject was conducted using the Centers for Disease Control (CDC) 2019‐nCoV real‐time reverse transcriptase (RT)‐PCR Diagnostic Panel assay. Descriptive statistics, Kaplan–Meier curve median event times and log‐rank tests were used to compare outcomes between groups. Results Ninety‐one children met inclusion criteria. Median age was 15.5 years (interquartile range [IQR] 8–18), 64% were male, 58% were White, and 43% were Hispanic/Latinx. Most (67%) were tested in outpatient settings and 58% were asymptomatic. The median time to two negative tests was 42 days (IQR 25.0–55.0), with no differences in median time by illness presentation or level of immunosuppression. Seven children had more than one sample available for repeat testing, and five of seven (71%) children had initial C T values of 6 weeks and moderate to high viral load.

Introduction/Objectives: We evaluated the length of time immunocompromised children (ICC) remain positive for SARS-CoV-2, identified factors associated with viral persistence and determined cycle threshold (CT) values of children with viral persistence as a surrogate of viral load. Methods: We conducted a retrospective cohort study of ICC at a pediatric hospital from March 2020-2021. Immunocompromised status was defined as primary, secondary or acquired due to medical comorbidities/immunosuppressive treatment. The primary outcome was time to first-of-two consecutive negative SARS-CoV-2 Polymerase chain reaction (PCR) tests at least 24 hours apart. Testing of sequential clinical specimens from the same subject was conducted using the Centers for Disease Control (CDC) 2019-nCoV Real-Time RT-PCR Diagnostic Panel assay. Descriptive statistics, Kaplan-Meier curve median event times and log-rank-sum tests were used to compare outcomes between groups. Results: Ninety-one children met inclusion criteria. Median age was 15.5 years (IQR 8-18 yrs), 64% were male, 58% were white, and 43% were Hispanic/Latinx. Most (67%) were tested in outpatient settings and 58% were asymptomatic. The median time to two negative tests was 42 days (IQR 25.0,55.0), with no differences in median time by illness presentation or level of immunosuppression. Seven children had >1 sample available for repeat testing, and 5/7 (71%) children had initial CT values of 6 weeks and moderate to high viral load.

Registered nurses (RNs) are national assets who provide quality patient care, especially during the corona virus disease 2019 pandemic. Currently, healthcare organizations are overwhelmed with ill patients who require RNs with specialty experiences. Curtailment and cancellation by healthcare organizations of civilian and military transition-to-practice programs for newly licensed RNs are at risk. If this phenomenon continues, current and future nursing shortages will prevail.

High-dose chemotherapy with autologous hematopoietic stem cell transplantation (autoHSCT) is a well-established treatment for pediatric central nervous system (CNS) tumors. Given the risks of toxicity and infection, pediatric autoHSCT has been historically performed on hospitalized children. As our practice evolved, some patients were transplanted as outpatients. We performed a retrospective cohort analysis of 37 patients who received 90 transplant procedures (49 outpatient and 41 inpatient) at Children’s Hospital Colorado. The most common primary diagnosis was medulloblastoma (51.4%). Of the patients transplanted as outpatients, 69.4% were admitted for fever and neutropenia and had a median time to hospitalization of day +6, with fever and neutropenia being the most common reasons for admission. The median time to neutrophil engraftment was the same in both cohorts, 11 days. Median time to platelet engraftment was 13 days (8–82 days) vs 16 days (8–106 days) (p = 0.0008). At day +100, the transplant-related mortality (TRM) was 0% for both the cohorts. At a median follow-up of 1.7 years, overall survival (OS) for all patients was 66.1% and TRM was 0% for both the cohorts. Outpatient autoHSCT for properly selected children with CNS tumors is safe and effective.