Project description:BackgroundListeriosis is a severe foodborne infection associated with high mortality. Pregnant women and newborns are at a particularly high risk of infection. However, the data on epidemiology of maternal-neonatal listeriosis in Xi'an are little known. The aim of this study was to investigate the epidemiological and clinical features of maternal-neonatal listeriosis in Xi'an.MethodsA total of 40 cases of listeriosis confirmed by positive cultures [blood or cerebrospinal fluid (CSF)] and admitted to the Northwest Women's and Children's Hospital (NWCH) from 2011 to 2020 were enrolled. Data from all patients were collected from the hospital's electronic medical records. Data analysis and epidemiological investigation were carried out by demographic information, time of onset, clinical and laboratory characteristics. Descriptive statistical indicators were obtained using SPSS21.0 and were expressed as median, mean, standard deviation and interquartile range.ResultsThe incidence of maternal and neonatal listeriosis in NWCH over the last decade was 5/100,000 and 10.4/100,000 respectively and Listeriosis was more likely to occur in spring and summer. The most common symptom was as follows: (I) maternal: fever (85%), abdominal pain (77%), vaginal fluid or colporrhagia (46%); (II) neonatal: respiratory distress (52%), fever (33%). Laboratary results were as follows: (I) maternal: elevated C-reactive protein (CRP) (100%), white blood cells (WBC) or neutrophil (NEUT#) (85%), and monocyte counts (MONO#) (77%); (II) neonatal: increased WBC (81%), MONO# (81%), CRP (78%), NEUT# and lymphocytes (73%); and elevated protein (PRO) (95%) and WBC count (86%) in CSF while decreased in glucose (GLU) (73%). Compared to neonatal group, the ratio of neutrophils to lymphocytes in maternal group raise to a higher level (92% to 42%). The outcomes of maternal were favorable and 54% of them suffered acute chorioamnionitism. Yet neonatal deaths account for up to 33%.ConclusionsListeriosis is a rare disease with extremely variable clinical characteristics in Xi'an. Our data indicated that unexplained fever, abdominal pain, signs of premature and respiratory symptoms accompanied by a progressive increase in WBC, CRP, NEUT#, MONO# even include WBC and PRO in CSF while GLU decreased, the possibility of an LM infection should be considered.

Project description:Abstract Delta-24-RGD (DNX-2401 in the clinic) has been tested for adult glioblastoma presenting a safe profile and promising efficacy. Our group has showed that the virus is safe and effective in preclinical models of pHGG and DIPG. Moreover, we showed that the virus is able to trigger an antitumor immune response. These results allowed us to propel a phase I clinical trial for newly diagnosed DIPGs (NCT03178032) where the patients received an intratumoral injection of DNX-2401 (N=12). Tumor biopsy is performed through the cerebellar peduncle, followed by virus injection using a cannula that prevents the reflux. The trial is uncontrolled, unicentric with a 3 + 3 design. The objective of this trial is to determine the safety, tolerability, and toxicity of DNX-2401 in subjects with DIPG. Secondary endpoints are overall survival at 12 months (OS12), percentage of responses and induced immune response against tumor. To date 9 patients have been treated within the trial. Three patients were treated with the D1=1x1010vp and because the lack of toxicity we escalated to the D2= 5x1010vp. The procedure was well tolerated and safe. Patients were home 3–4 days after the injection. All the patients displayed a reduced tumor volume after combined treatment. We performed molecular studies in 8 out of the 9 patients (RNAseq and a thermofisher pediatric panel). Subsequently we evaluated the immune cell composition in the tumor using multiplexed quantitative immunofluorescence on the biopsies pre-virus injection. T cells were hardly noticeable in these tumors while macrophages were abundant. Using a multiplexed TCR-sequencing mRNA-based assay to analyze 18 available paired pre- and post-treatment samples from the trial, we detected increased clonal T cell diversity following treatment with virus. In addition, we are assessing the existence of pre and post treatment neutralizing antibodies and its relationship with survival. Finally, we have performed functional studies using 2 cell lines isolated from patients included in this trials and confronting them with T-cells isolated from peripheral blood of the same patients before and after the treatment with the virus. Information acquired within this clinical study would aid to understand the response of DIPGs to viral therapies and therefore to better tailor this strategy to improve the survival of pediatric brain tumors.

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Ena-DATASET-UHN-03-11-2020-18:27:13:290-158 - samples

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