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

Determination of nutrient salts by automatic methods both in seawater and brackish water: the phosphate blank

9 páginas, 2 tablas, 2 figurasThe main inconvenience in determining nutrients in seawater by automatic methods is simply solved: the preparation of a suitable blank which corrects the effect of the refractive index change on the recorded signal. Two procedures are proposed, one physical (a simple equation to estimate the effect) and the other chemical (removal of the dissolved phosphorus with ferric hydroxide).Support for this work came from CICYT (MAR88-0245 project) and Conselleria de Pesca de la Xunta de GaliciaPeer reviewe

40 Long-term clinical outcome of functional tricuspid regurgitation

Abstract Background Significant functional tricuspid regurgitation (TR) has been associated with higher risk for adverse cardiovascular outcomes. Left-sided heart disease (LHD) is a potentially important confounder of this association because it is strongly linked to both TR and to clinical outcome. Methods We studied 5886 patients who were followed for a period of 10-years after the index echocardiographic examination. The relationship between TR severity and the composite endpoint of admission for heart failure or cardiovascular mortality was analyzed using a Cox model. An additional analysis included a propensity-score-matching. To simplify the modeling of the severity of LHD, we calculated an additive score summing the number of LHD components as follows: reduced LVEF, LA enlargement ≥moderate, aortic or mitral valve disease (regurgitation or stenosis ≥moderate) and PASP≥50 mmHg. Results Higher TR grade was associated with markers of LHD including left ventricular systolic dysfunction, valvular heart disease ≥moderate, left atrial enlargement and pulmonary hypertension (All P &amp;lt; 0.001). There was a significant interaction between TR and the presence of LHD with regard to the endpoint of heart failure in the model for admission for heart failure (P = 0.01) and the combined endpoint of heart failure and cardiovascular mortality (P = 0.02). In both models, moderate/severe TR was associated with higher risk for heart failure (hazard ratio [HR] 3.13; 95% CI 2.49–3.93, P &amp;lt; 0.0001) and the combined endpoint of heart failure or cardiovascular mortality (HR 2.61; 95% CI 1.33–5.13, P = 0.005) only in patients without LHD. The interaction plot (Figure) demonstrates that when LHD is present, TR is not a predictor of clinical outcome. Propensity score matching yielded 350 patient pairs, of which 88% had LHD. The HR for heart failure or cardiovascular mortality at 10-years was 0.78 (95% CI 0.56–1.08, P = 0.14) in the moderate/severe TR as compared with the trivial/mild TR. Conclusions Moderate or severe functional TR portends an increased risk for heart failure and cardiovascular mortality only when isolated, without concomitant LHD. Abstract 40 Figure. Interaction plot </jats:sec

44 Determinants of functional tricuspid regurgitation progression

Abstract Background Tricuspid regurgitation has been the focus of increasing interest and research in recent years. However, few data are available with regard to risk factors associated with the evolution of TR. purpose The aimed to determine the risk factors for the development of hemodynamically significant functional TR. Methods We studied 1552 subjects with an index echocardiogram demonstrating trivial or mild TR. Risk factors for TR progression to moderate or severe TR during a median follow-up time of 38 months (IQR 26 to 63 months), were determined using logistic regression. Results In the multivariable logistic regression model, older age, female gender, pacemaker electrode and indicators of left heart disease (LA enlargement, increased pulmonary artery pressure (PAP), atrial fibrillation, and left-sided valvular disease) were associated with future development moderate or severe TR (Table). The strongest predictors of TR progression were PAP, LA size, AF, and age. The final echocardiographic examination demonstrated a marked worsening in the severity of left-sided myocardial and valvular disease, that was more prominent in subjects with TR progression (Figure). Compared with subjects in whom TR did not progress, subjects with TR progression demonstrated an increase in PAP and in the severity of mitral and aortic valve disease, larger increases in LA and reductions in LVEF (Figure). Lager proportions of subjects progressing to significant TR developed AF, were implanted with pacemakers or defibrillators or underwent valvular interventions (Figure). The mean PAP change between the baseline and final echocardiographic examination was 16 ± 15 mm Hg and 3 ± 11 mm Hg with and without TR progression, respectively (P &amp;lt; 0.0001). Conclusion Predictors of TR progression are mostly indicators of more advanced left heart disease. In addition, progression to significant TR is associated with a more acceleration course of left hear disease. Independent Predictors of TR Progression Characteristics HR (95% CI) P value Age (per 10 years increase) 1.35 (1.31-1.50) &amp;lt;0.0001 Female sex 1.50 (1.13-1.99) &amp;lt;0.0001 Heart failure 2.76 (1.43-5.32) 0.002 LA enlargement ≥ Moderate 1.86 (1.29-2.67) 0.001 Atrial fibrillation 2.34 (1.57-3.49) &amp;lt;0.0001 Pacemaker/ICD 2.93 (1.48-5.78) 0.002 Pulmonary artery pressure (per 10 mm Hg increase) 1.47 (1.29-1.69) &amp;lt;0.0001 Valvular heart disease≥ Moderate 1.50 (1.11-2.04) 0.009 Abstract 44 Figure. Proportion of new abnormalities </jats:sec