Characteristics and outcomes of neonatal SARS-CoV-2 infection in the UK: a prospective national cohort study using active surveillance.

BACKGROUND: Babies differ from older children with regard to their exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, data describing the effect of SARS-CoV-2 in this group are scarce, and guidance is variable. We aimed to describe the incidence, characteristics, transmission, and outcomes of SARS-CoV-2 infection in neonates who received inpatient hospital care in the UK. METHODS: We carried out a prospective UK population-based cohort study of babies with confirmed SARS-CoV-2 infection in the first 28 days of life who received inpatient care between March 1 and April 30, 2020. Infected babies were identified through active national surveillance via the British Paediatric Surveillance Unit, with linkage to national testing, paediatric intensive care audit, and obstetric surveillance data. Outcomes included incidence (per 10 000 livebirths) of confirmed SARS-CoV-2 infection and severe disease, proportions of babies with suspected vertically and nosocomially acquired infection, and clinical outcomes. FINDINGS: We identified 66 babies with confirmed SARS-CoV-2 infection (incidence 5·6 [95% CI 4·3-7·1] per 10 000 livebirths), of whom 28 (42%) had severe neonatal SARS-CoV-2 infection (incidence 2·4 [1·6-3·4] per 10 000 livebirths). 16 (24%) of these babies were born preterm. 36 (55%) babies were from white ethnic groups (SARS-CoV-2 infection incidence 4·6 [3·2-6·4] per 10 000 livebirths), 14 (21%) were from Asian ethnic groups (15·2 [8·3-25·5] per 10 000 livebirths), eight (12%) were from Black ethnic groups (18·0 [7·8-35·5] per 10 000 livebirths), and seven (11%) were from mixed or other ethnic groups (5·6 [2·2-11·5] per 10 000 livebirths). 17 (26%) babies with confirmed infection were born to mothers with known perinatal SARS-CoV-2 infection, two (3%) were considered to have possible vertically acquired infection (SARS-CoV-2-positive sample within 12 h of birth where the mother was also positive). Eight (12%) babies had suspected nosocomially acquired infection. As of July 28, 2020, 58 (88%) babies had been discharged home, seven (11%) were still admitted, and one (2%) had died of a cause unrelated to SARS-CoV-2 infection. INTERPRETATION: Neonatal SARS-CoV-2 infection is uncommon in babies admitted to hospital. Infection with neonatal admission following birth to a mother with perinatal SARS-CoV-2 infection was unlikely, and possible vertical transmission rare, supporting international guidance to avoid separation of mother and baby. The high proportion of babies from Black, Asian, or minority ethnic groups requires investigation. FUNDING: UK National Institute for Health Research Policy Research Programme

Short-course antibiotics for chemotherapy-induced febrile neutropaenia : Retrospective cohort study

Background: Recent research in febrile neutropaenia (FN) has focused on reducing the intensity of treatment for those thought to be at low risk of significant morbidity or mortality. This has not led to a reduced burden of treatment for either families or healthcare systems. An alternative approach is to discharge all patients who remain well after 48 hours of inpatient treatment, either with no ongoing treatment or with appropriate antibiotics if the cultures are positive. This paper aimed to demonstrate that this approach is safe. Methods: Patients treated according to this approach in a single centre were reviewed retrospectively, with a random selection of patients from a 4-year period. Data were collected according to the Predicting Infectious Complications of Neutropenic sepsis in Children with Cancer dataset. In addition, all septic deaths over a 10-year period were reviewed in the same manner. Results: 179 episodes of FN were reviewed from 47 patients. In 70% (125/179) of episodes, patients were discharged safely once 48-hour microbiology results were available, with only 5.6% (7/125) resulting in readmission in the 48 hours following discharge. There were no septic deaths in this cohort. There were 11 deaths due to FN over the 10-year study period. Almost all patients were identified as severely unwell in the early stages of their final presentation or had a prolonged final illness. Conclusion: This paper indicates that the policy described provides a balance between safety and acceptability. Further work is needed to demonstrate non-inferiority and cost-benefit

Additional file 7: of Access to principal treatment centres and survival rates for children and young people with cancer in Yorkshire, UK

Table S6. Hazard ratios (HR) for patient case-mix variables for bone tumours and soft tissue sarcomas (DOCX 28.8 kb

What the Mark and Mirror Test reflects (review)

This thesis deals with the use of a mirror test to determine the cognitive abilities of animals. An overview is given of the mirror test for cetaceans, primates and proboscideans. The conclusion states the appropriateness of applying this test to the biology of the species

Additional file 5: of Access to principal treatment centres and survival rates for children and young people with cancer in Yorkshire, UK

Table S4. Hazard ratios for multivariable Cox regression models by level of treatment at PTC and diagnostic group for TYA only (DOCX 25 kb

Increased Replication Stress Determines ATR Inhibitor Sensitivity in Neuroblastoma Cells

Despite intensive high-dose multimodal therapy, high-risk neuroblastoma (NB) confers a less than 50% survival rate. This study investigates the role of replication stress in sensitivity to inhibition of Ataxia telangiectasia and Rad3-related (ATR) in pre-clinical models of high-risk NB. Amplification of the oncogene MYCN always imparts high-risk disease and occurs in 25% of all NB. Here, we show that MYCN-induced replication stress directly increases sensitivity to the ATR inhibitors VE-821 and AZD6738. PARP inhibition with Olaparib also results in replication stress and ATR activation, and sensitises NB cells to ATR inhibition independently of MYCN status, with synergistic levels of cell death seen in MYCN expressing ATR- and PARP-inhibited cells. Mechanistically, we demonstrate that ATR inhibition increases the number of persistent stalled and collapsed replication forks, exacerbating replication stress. It also abrogates S and G2 cell cycle checkpoints leading to death during mitosis in cells treated with an ATR inhibitor combined with PARP inhibition. In summary, increased replication stress through high MYCN expression, PARP inhibition or chemotherapeutic agents results in sensitivity to ATR inhibition. Our findings provide a mechanistic rationale for the inclusion of ATR and PARP inhibitors as a potential treatment strategy for high-risk NB