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

Commercial fishing patterns influence odontocete whale-longline interactions in the Southern Ocean

The emergence of longline fishing around the world has been concomitant with an increase in depredation-interactions by odontocete whales (removal of fish caught on hooks), resulting in substantial socio-economic and ecological impacts. The extent, trends and underlying mechanisms driving these interactions remain poorly known. Using long-term (2003–2017) datasets from seven major Patagonian toothfish (Dissostichus eleginoides) longline fisheries, this study assessed the levels and inter-annual trends of sperm whale (Physeter macrocephalus) and/or killer whale (Orcinus orca) interactions as proportions of fishing time (days) and fishing area (spatial cells). The role of fishing patterns in explaining between-fisheries variations of probabilities of odontocete interactions was investigated. While interaction levels remained globally stable since the early 2000s, they varied greatly between fisheries from 0 to >50% of the fishing days and area. Interaction probabilities were influenced by the seasonal concentration of fishing effort, size of fishing areas, density of vessels, their mobility and the depth at which they operated. The results suggest that between-fisheries variations of interaction probabilities are largely explained by the extent to which vessels provide whales with opportunities for interactions. Determining the natural distribution of whales will, therefore, allow fishers to implement better strategies of spatio-temporal avoidance of depredation.</p

Salinity and sensitivity to endocrine disrupting chemicals: A comparison of reproductive endpoints in small-bodied fish exposed under different salinities

The influence of salinity on toxicity outcomes has been demonstrated for various contaminants, but has received limited attention for endocrine disrupting chemicals (EDCs). Short-term laboratory tests using small-bodied fish are an important tool for evaluating impacts of EDCs on reproduction. Tests have been developed for both freshwater and estuarine/marine species, providing an opportunity to assess whether concentrations at which small-bodied fish respond to EDCs may be influenced by salinity. We conducted a semi-quantitative review of short-term laboratory tests with small-bodied fish exposed to EDCs, including 59 studies under freshwater conditions (7 species) and 23 studies conducted under saline conditions (5 species). We focused on two model estrogens [17α-ethinylestradiol and 17β-estradiol (E2)], and three androgens (17β-trenbolone, 5α-dihydrotestosterone and 17α-methyltestosterone). The lowest observed adverse effect concentration (LOAECLOW) for key reproductive endpoints was recorded, including sex-steroid and vitellogenin (VTG) levels, fecundity and fertilization. In 65.2% of cases, responses occurred at lower doses under freshwater compared to saline conditions, compared to only 4.3% of cases where fish responded to lower doses under saline conditions. The potential influence of salinity was more pronounced when estrogenic compounds were considered separately, with fish responding to lower doses under fresh compared to saline conditions in 90.5% of cases. Fecundity and E2 level were identified as the most sensitive endpoints for evaluating EDCs regardless of salinity. Interestingly, female VTG levels were a sensitive endpoint under freshwater but not saline conditions. Overall, our results suggest that salinity may be an important factor influencing how small-bodied fish respond to environmental EDCs.Full Tex