Objectives Concentrations of endothelin I (ET1) are elevated in CHF patients, and, like other biomarkers that reflect hemodynamic status and cardiac pathophysiology, are prognostic. The Singulex assay (Sgx-ET1) measures the active form of ET1, with a short in-vivo half-life and C-terminal endothelin-1 (CT-ET1) is measured by the Brahms assay and is a modified (degraded) product with longer half-life. We aimed to determine the prognostic importance of active and modified forms of endothelin 1 (Singulex and Brahms assays) in comparison with other commonly measured biomarkers of inflammation, hemodynamic status and cardiac physiology in CHF. Design & Methods Plasma biomarkers (Sgx-ET1, CT-ET1, NTproBNP, IL-6, TNFα, cTnI, VEGF, hs-CRP, Galectin-3, ST2) were measured in 134 NYHA class II and III CHF patients with systolic dysfunction. Prognostic importance of biomarkers for hospitalization or death were calculated by both logistic regression and Kaplan-Meier survival analyses. Results CT-ET1 (OR 5.2, 95% CI 1.7–15.7) and Sgx-ET1 (OR 2.9, CI 1.1–7.7) were independent predictors of hospitalization and death and additively predicted events after adjusting for age, sex and other significant biomarkers. Other biomarkers did not improve the model. Similarly, in Cox regression analysis, only CT-ET1 (HR 3.4, 95% CI 1.4–8.4), VEGF (2.7, 95% CI 1.3–5.4) and Sgx-ET1 (HR 2.6, 95% CI 1.2–5.6) were independently prognostic. Conclusions Elevated concentrations of endothelin 1 predict mortality and hospitalizations in HF patients. Endothelin 1 was more prognostic than commonly obtained hemodynamic, inflammatory and fibrotic biomarkers. Two different assays of endothelin 1 independently and synergistically were prognostic, suggesting either complementary information or extreme prognostic importance.

Objective Standard predictors do not fully explain variations in the frequency and timing of heart failure (HF) adverse events (AEs). Psychological stress can trigger acute cardiovascular (CV) events, but it is not known whether stress can precipitate AEs in HF patients. We investigated prospective associations of psychological stress with AEs in patients with HF. Methods 144 HF patients (77% male; 57.5±11.5, range 23–87 years, LVEF≤40%) were longitudinally evaluated for psychological stress (Perceived Stress Scale; PSS) and AEs (CV hospitalizations/death) at 2-week intervals for 3 months, and at 9-month follow- up. Results 42 patients (29.2%) had at least one CV hospitalization and 9 (6.3%) died. Patients reporting high average perceived stress across study measurements had a higher likelihood of AEs during the study period compared to those with lower stress (OR=1.10, 95% CI=1.04, 1.17). In contrast to average levels, increases in stress did not predict AEs (p=.96). Perceived stress was elevated after a CV hospitalization (B=2.70, SE=0.93, p=.004) suggesting that CV hospitalizations increase stress. Subsequent analysis indicated that (24 of 38; 63%) of patients showed a stress increase following hospitalization. However, a prospective association between stress and AEs was present when accounting for prior hospitalizations (B=2.43, SE=1.23, p=.05). Conclusions Sustained levels of perceived stress are associated with increased risk of AEs, and increased distress following hospitalization occurs in many, but not all, HF patients. Patients with chronically high stress may be an important target group for HF interventions aimed at reducing hospitalizations.

No abstract

Calf diarrhea is the most common reason for mortality and antimicrobial therapy in preweaned calves on dairy farms in the United States. Conventional and organic livestock producers require alternative therapies for calf diarrhea to reduce the necessity of conventional antimicrobials. Alternatives administered for mild cases or early in the disease course may be useful to mitigate disease progression and reduce the likelihood of septicemia and negative sequelae. Lactoferrin is a bioactive protein naturally found in colostrum that has been shown to prevent septicemia in high-risk infants. Among organic producers, garlic extract is widely used for the treatment of disease and perceived to be efficacious. The objectives of the study were to determine the effectiveness of lactoferrin and garlic extract to reduce mortality and culling, improve weight gain, and reduce the duration of disease in preweaned calves with the first diagnosis of diarrhea. In total, 628 calves with diarrhea from a single commercial dairy were enrolled in a blinded, randomized field trial. Calves diagnosed with diarrhea (fecal score ≥3), were randomized to 3 consecutive days of oral garlic extract, lactoferrin, or water (control). Calves were clinically evaluated for up to 10 d. Body weight was measured at enrollment and 10 d later. For calves receiving garlic extract, the risk of death or culling was not significantly different than calves in the control group; however, calves that received lactoferrin had approximately half the risk of death or culling in the 120 d following diagnosis. Additionally, the relative risk of death or culling in the 60 d following diagnosis was significantly lower for the subset of calves with severe diarrhea at enrollment. Neither garlic nor lactoferrin had a significant effect on disease duration or average weight gain during the 10-d period. Lactoferrin significantly reduced mortality and culling when administered to preweaned calves with the first diagnosis of diarrhea; however, additional studies conducted across multiple farms are necessary to corroborate the observed reduction in mortality and culling. If the results are confirmed, lactoferrin may become an important tool to improve treatment outcomes and reduce the necessity of antimicrobials.