Neonatal Sepsis: A Review of Pathophysiology and Current Management Strategies.

BACKGROUND: Early-onset sepsis, occurring within 72 hours of birth, and late-onset sepsis, occurring after this time period, present serious risks for neonates. While culture-based screening and intrapartum antibiotics have decreased the number of early-onset cases, sepsis remains a top cause of neonatal morbidity and mortality in the United States. PURPOSE: To provide a review of neonatal sepsis by identifying its associated risk factors and most common causative pathogens, reviewing features of the term and preterm neonatal immune systems that increase vulnerability to infection, describing previous and the most current management recommendations, and discussing relevant implications for the neonatal nurse and novice neonatal nurse practitioner. METHODS/SEARCH STRATEGY: An integrative review of literature was conducted using key words in CINAHL, Google Scholar, and PubMed. FINDINGS/RESULTS: Group B streptococcus and Escherichia coli are the most common pathogens in early-onset sepsis, while Coagulase-negative staphylococci comprise the majority of cases in late-onset. The neonatal immune system is vulnerable due to characteristics including decreased cellular activity, underdeveloped complement systems, preferential anti-inflammatory responses, and insufficient pathogenic memory. Blood cultures remain the criterion standard of diagnosis, with several other adjunct tests under investigation for clinical use. The recent development of the sepsis calculator has been a useful tool in the management of early-onset cases. IMPLICATIONS FOR PRACTICE: It is vital to understand the mechanisms behind the neonate's elevated risk for infection and to implement evidence-based management. IMPLICATIONS FOR RESEARCH: Research needs exist for diagnostic methods that deliver timely and sensitive results. A tool similar to the sepsis calculator does not exist for preterm infants or late-onset sepsis, groups for which antibiotic stewardship is not as well practiced.Video Abstract available athttps://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?autoPlay=false&videoId=40.

Perinatal Bacterial Exposure Contributes to IL-13 Aeroallergen Response.

There is a high prevalence of aeroallergen sensitivity in asthmatic populations, and seroreactivity to aeroallergens early in infancy is associated with increased risk of developing asthma later in life. In addition to allergen sensitivity, asthma development has been associated with differential microbial exposure and infection in early life. We have previously shown that cord blood mononuclear cells respond to common aeroallergens (i.e., house dust mite [Der f1] and cockroach [Bla g2]) as assayed by lymphoproliferation and cytokine (IL-13 and IFN-γ) production. We hypothesized that there is a relationship between perinatal microbial exposure and response to specific aeroallergens. To test this hypothesis, we isolated DNA from cord blood serum samples with known lymphoproliferative and cytokine responses to Bla g2 and Der f1. Bacterial 16S ribosomal DNA amplicon libraries were generated and analyzed using high throughput sequencing of cord blood serum samples. In our analysis, we identified major compositional differences, including diversity and abundance of specific taxa, between groups whose IL-13 response to Der f1 and Bla g2 differed. We demonstrate a strong association between the ratio of Acinetobacter to Proteobacteria and IL-13 production and the probability of IL-13 production after allergen exposure. IL-13 concentrations in serum were also significantly correlated with the diversity of bacterial DNA. Together, these results underscore the relationship between immune responses to allergens and bacterial exposure during perinatal development.

The impact of Oncotype DX testing on breast cancer management and chemotherapy prescribing patterns in a tertiary referral centre.

INTRODUCTION: The use of chemotherapy in node-negative, (O)Estrogen Receptor (ER)-positive breast cancer has changed significantly since the introduction of Oncotype DX to determine systemic recurrence risk based on tumour genomic signature. AIMS: This study aims to METHODS: A cohort study was undertaken, including consecutive patients with early node-negative, ER-positive breast cancer diagnosed between 2006 and May 2013, including a period of prospective clinical trial (Trial Assigning Individualised Options for Treatment (TAILORx)) recruitment. Data were collected regarding patient demographics, tumour clinico-pathological features, Oncotype DX use and recurrence score and chemotherapy use. All therapeutic decisions were made following multidisciplinary discussion, with adherence to guidelines and consideration of trial protocol and Oncotype DX recurrence scores. RESULTS: 479 consecutive patients were included in the study, of whom 241 (50%) underwent Oncotype DX testing, 97 as part of the TAILORx clinical trial. Oncotype DX testing began on a trial basis in 2007 and until October 2011, only patients enrolled on TAILORx availed of genomic profiling. From October 2011, Oncotype DX was used in all eligible patients as per National Cancer Control Programme (NCCP) guidelines. A total of 216 (45%) patients received chemotherapy. The use of chemotherapy changed in inverse proportion to the availability of the genomic assay. Of those patients in whom Oncotype DX was utilised, 138 (57%) were spared chemotherapy. CONCLUSION: This study validates the use of molecular testing in the rationalisation of systemic therapy.