Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Metastatic choriocarcinoma induced separate simultaneous intracerebral haemorrhages: a very rare occurrence and its novel association with Klinefelter syndrome

Non-traumatic separate simultaneous intracerebral haemorrhages (SSIHs) are rare. Relevant aetiologies are diverse and their diagnosis challenging. We report a unique case of SSIH in an 18-year-old male with a background of previously undiagnosed testicular choriocarcinoma and Klinefelter syndrome. The patient was admitted to Auckland City Hospital with headaches, drowsiness and vomiting. A CT scan revealed SSIH in a background of tumorous lesions. His β human chorionic gonadotropin titre was elevated at 355 000 IU/L. The SSIH and the associated tumorous lesions were acutely surgically resected and the patient started on bleomycin, etoposide and cisplatin combination chemotherapy with excellent results. In this article, we underline choriocarcinoma as a rare aetiology of SSIH and present an example of the clinical presentation, investigation and management of this very rare pathological entity

Scientific Opinion on welfare aspects of the use of perches for laying hens

This opinion investigated the use of perches for laying hens in cage and non-cage systems. It is based on various activities reviewing the effects of perch height and design on hen health and welfare. Systematic and extensive literature reviews were conducted to assess the scientific evidence about hen motivation to grasp and seek elevation, and the appropriate height of perches as well as other features (position, material, colour, temperature, shape, width and length). In addition, an expert knowledge elicitation (EKE) exercise was run with technical hearing experts to discuss and prioritise the various design aspects of perches. Overall, the body of literature on perches is limited. Relevant features of perches are often confounded with others. In the literature, the most commonly used animal-based measures to assess perch adequacy are keel bone damages, foot pad lesions and perch use by hens. Overall, hens seek elevation during the day as well as during the night, when they select a site for roosting. Elevated perches allow hens to monitor the environment, to escape from other hens, avoid disturbances and improve thermoregulation. For night-time roosting hens show a preference for perches higher than 60cm compared with lower perches. However, elevated perches can have negative consequences with increased prevalence of keel deformities and fractures. The risk of injury increases when hens have to jump a distance of more than 80cm vertically, horizontally or diagonally to reach or leave a perch, or jump an angle between 45 and 90\ub0 (measured at the horizontal plane). Material, shape, length and width of the perch also influence perch preference by hens. The EKE exercise suggests that an adequate perch is elevated, accessible and functional (providing sufficient overview). The opinion concludes that for the design of an adequate perch, different features of perches need to be further investigated and integrated

Moving to the Beat: Using Music, Rhythm, and Movement to Enhance Self-Regulation in Early Childhood Classrooms

Differences in early self-regulation skills contribute to disparities in success in early learning and school transition, as well as in childhood wellbeing. Self-regulation refers to managing emotional, cognitive and behavioral processes that are conducive to positive adjustment and social relationships. Researchers have identified that various domains of learning and development are enhanced by musical training, and understanding about the neurological processes responsible for such effects is increasing. This paper argues that coordinated rhythmic movement activities in preschool are an effective approach to support the neurological bases of self-regulation. Evidence and theory related to beat synchronization, cognitive benefits of formal music training, and music therapy for clinical populations are discussed to argue that musical activities could be better leveraged in early childhood education. The paper concludes that preschool activities designed to stimulate beat synchronization and motor coordination skills, and embedded in group activities can enhance young children’s motor, auditory, and self-regulatory functioning