Wademaclean5458

001). Residents cited time constraints, lack of knowledge about available resources, and discomfort with screening questions as barriers to screening in both settings. Residents were more likely to screen for social needs when screening questions were embedded in the EHR (odds ratio = 9.6; 95% confidence interval 6.7-13.9). CONCLUSIONS Pediatric residents were more likely to screen for unmet social needs in the outpatient than in the inpatient setting despite reporting similar barriers to screening in both settings. EHR-based social needs screening templates could be used to increase rates of screening and reach additional families in need. Copyright © 2020 by the American Academy of Pediatrics.Immune checkpoint inhibitors (ICIs) are now routinely used in multiple cancers but may induce autoimmune-like side effects known as immune-related adverse events (irAEs). Although classical autoimmune diseases have well-known risk factors, including age, gender, and seasonality, the clinical factors that lead to irAEs are not well-defined. To explore these questions, we assessed 455 patients with advanced melanoma treated with ICI at our center and a large pharmacovigilance database (Vigibase). We found that younger age was associated with a similar rate of any irAEs but more frequent severe irAEs and more hospitalizations (OR 0.97 per year). Paradoxically, however, older patients had more deaths and increased length of stay when hospitalized. This was partially due to a distinct toxicity profile colitis and hepatitis were more common in younger patients, whereas myocarditis and pneumonitis had an older age distribution both in our center and in Vigibase. This pattern was particularly apparent with combination checkpoint blockade with ipilimumab and nivolumab. We did not find a link between gender or seasonality on development of irAEs in univariate or multivariate analyses, although winter hospitalizations were associated with marginally increased length of stay. This study identifies age-specific associations of irAEs. Copyright ©2020, American Association for Cancer Research.Proneural-to-mesenchymal transition (PMT) is a common process in glioblastoma (GBM) progression that leads to increased radiotherapy resistance. However, the mechanism underlying PMT is poorly understood. Here, we found that tumor-associated macrophages (TAMs) triggered PMT in glioma stem cells (GSCs) via small extracellular vesicles (sEVs). sEVs from monocyte-derived macrophages transferred miR-27a-3p, miR-22-3p and miR-221-3p to GSCs, and these microRNAs (miRs) promoted several mesenchymal (MES) phenotypes in proneural(PN) GSCs by simultaneously targeting CHD7. We found that CHD7 played a critical role in the maintenance of the PN phenotype and CHD7 knockdown significantly promoted PMT in GSCs via the RelB/P50 and p-STAT3 pathways. The induction of PMT by sEVs containing miR-27a-3p, miR-22-3p and miR-221-3p in a xenograft nude mouse model exacerbated radiotherapy resistance and thus decreased the benefits of radiotherapy. Collectively, these findings identified macrophage-derived sEVs (MDEs) as key regulators of PMT in GSCs and demonstrated that CHD7 is a novel inhibitor of PMT. Copyright ©2020, American Association for Cancer Research.SUMMARYIntrathecal administration of anti-infectives is indicated in central nervous system infections by multiresistant pathogens when drugs that can reach adequate cerebrospinal fluid (CSF) concentrations by systemic therapy are not available. Antibiotics that readily pass the blood-brain and blood-CSF barriers and/or that have low toxicity allowing an increase in the daily dosage should not be used for intrathecal therapy. Intrathecal therapy is accompanied by systemic treatment. Antibacterials indispensable for intrathecal therapy include aminoglycosides, colistin, daptomycin, tigecycline, and vancomycin. Limited experience suggests the utility of the antifungals amphotericin B and caspofungin. Galunisertib mouse Intraventricular administration ensures distribution throughout the CSF compartment, whereas intralumbar dosing often fails to attain adequate antibiotic concentrations in the ventricles. The individual dose is determined by the estimated size of the CSF space and by the estimated clearance from CSF. For moderately lipophilic anti-infectives with a molecular weight above approximately 1,000 g/mol, as well as for hydrophilic drugs with a molecular weight above approximately 400 g/mol, one daily dose is normally adequate. The ventricular drain should be clamped for 15 to 120 min to facilitate the distribution of the anti-infective in the CSF space. Therapeutic drug monitoring of the trough levels is necessary only in cases of therapeutic failure. Copyright © 2020 American Society for Microbiology.SUMMARYAlthough not as ubiquitous as antibacterial susceptibility testing, antifungal susceptibility testing (AFST) is a tool of increasing importance in clinical microbiology laboratories. The goal of AFST is to reliably produce MIC values that may be used to guide patient therapy, inform epidemiological studies, and track rates of antifungal drug resistance. There are three methods that have been standardized by standards development organizations broth dilution, disk diffusion, and azole agar screening for Aspergillus Other commonly used methods include gradient diffusion and the use of rapid automated instruments. Novel methodologies for susceptibility testing are in development. It is important for laboratories to consider not only the method of testing but also the interpretation (or lack thereof) of in vitro data. Copyright © 2020 American Society for Microbiology.BACKGROUND Pregnancy in women with type 1 diabetes mellitus (T1DM) is associated with an increased risk of congenital malformations, obstetric complications and neonatal morbidity. This study aims to investigate maternal, perinatal and neonatal outcomes of pregnancies in women with onset of T1DM less than 18 years of age. METHODS This retrospective cohort study extracted data regarding prenatal, intrapartum and postnatal outcomes of pregnancies in women with onset of T1DM less then 18 years identified from the diabetes in pregnancy register at University Maternity Hospital Limerick, treated from July 1, 2007 to July 1, 2017. RESULTS Seventeen women with onset of T1DM less then 18 years gave birth to 23 live infants during the period studied. 73.9% of pregnancies were unplanned. Only 21.7% of pregnancies took preconceptual folic acid. 60.9% of infants required treatment for hypoglycemia. CONCLUSION The high prevalence of unplanned pregnancy and poor uptake of prepregnancy care must be improved on in order to improve outcomes for this high-risk group.