Presenza e distribuzione di specie ittiche esotiche (Pisces: Osteichthyes) nel bacino del Fiume Tevere, dalle sorgenti alla confluenza con il Fiume Nera

Volume: 137Start Page: 47End Page: 6

Are Baseline Levels of Gas6 and Soluble Mer Predictors of Mortality and Organ Damage in Patients with Sepsis? The Need-Speed Trial Database

Soluble tyrosine kinase receptor Mer (sMer) and its ligand Growth arrest-specific protein 6 (Gas6) are predictors of mortality in patients with sepsis. Our aim is to clarify whether their measurement at emergency department (ED) presentation is useful in risk stratification. We re-analyzed data from the Need-Speed trial, evaluating mortality and the presence of organ damage according to baseline levels of sMer and Gas6. 890 patients were eligible; no association with 7- and 30-day mortality was observed for both biomarkers (p > 0.05). sMer and Gas6 levels were significantly higher in acute kidney injury (AKI) patients compared to non-AKI ones (9.8 [4.1-17.8] vs. 7.9 [3.8-12.9] ng/mL and 34.8 [26.4-47.5] vs. 29.8 [22.1-41.6] ng/mL, respectively, for sMer and Gas6), and Gas6 also emerged as an independent AKI predictor (odds ratio (OR) 1.01 [1.00-1.02]). Both sMer and Gas6 independently predicted thrombocytopenia in sepsis patients not treated with anticoagulants (OR 1.01 [1.00-1.02] and 1.04 [1.02-1.06], respectively). Moreover, sMer was an independent predictor of both prothrombin time-international normalized ratio (PT-INR) > 1.4 (OR 1.03 [1.00-1.05]) and sepsis-induced coagulopathy (SIC) (OR 1.05 [1.02-1.07]). An early measurement of the sMer and Gas6 plasma concentration could not predict mortality. However, the biomarkers were associated with AKI, thrombocytopenia, PT-INR derangement and SIC, suggesting a role in predicting sepsis-related organ damage

The Role of Mid-Regional Proadrenomedullin in the Differential Diagnosis between Culture-Negative and Culture-Positive Sepsis at Emergency Department Admission

Background: The host response in culture-negative sepsis (CnS) has been marginally explored upon emergency department (ED) admission. It would be of paramount importance to create a clinical prediction rule to support the emergency department physician in identifying septic patients who can be treated with antibiotics immediately without waiting time to draw cultures if they are unlikely to provide useful diagnostic information. Methods: A multivariable logistic regression analysis was applied to identify the independent clinical variables and serum biomarkers of the culture-negative status among 773 undifferentiated septic patients. Those predictors were combined to build a nomogram predictive of CnS. Results: The serum concentrations of six biomarkers, among the eight biomarkers assayed in this study, were significantly lower in the patients with CnS (449) than in those with culture-positive sepsis (324). After correction for co-variates, only mid-regional proadrenomedullin (MR-proADM) was found to be independently correlated with culture-negative status. Absence of diabetes, hemoglobin concentrations, and respiratory source of infection were the other independent clinical variables integrated into the nomogram—its sensitivity and specificity for CnS were 0.80 and 0.79, respectively. Conclusions: Low concentrations of MR-proADM were independently associated with culture-negative sepsis. Our nomogram, based on the MR-proADM levels, did not predict culture-negative status with reasonable certainty in patients with a definitive diagnosis of sepsis at ED admission.</jats:p

The Role of Mid-Regional Proadrenomedullin in the Differential Diagnosis between Culture-Negative and Culture-Positive Sepsis at Emergency Department Admission

Background: The host response in culture-negative sepsis (CnS) has been marginally explored upon emergency department (ED) admission. It would be of paramount importance to create a clinical prediction rule to support the emergency department physician in identifying septic patients who can be treated with antibiotics immediately without waiting time to draw cultures if they are unlikely to provide useful diagnostic information. Methods: A multivariable logistic regression analysis was applied to identify the independent clinical variables and serum biomarkers of the culture-negative status among 773 undifferentiated septic patients. Those predictors were combined to build a nomogram predictive of CnS. Results: The serum concentrations of six biomarkers, among the eight biomarkers assayed in this study, were significantly lower in the patients with CnS (449) than in those with culture-positive sepsis (324). After correction for co-variates, only mid-regional proadrenomedullin (MR-proADM) was found to be independently correlated with culture-negative status. Absence of diabetes, hemoglobin concentrations, and respiratory source of infection were the other independent clinical variables integrated into the nomogram&mdash;its sensitivity and specificity for CnS were 0.80 and 0.79, respectively. Conclusions: Low concentrations of MR-proADM were independently associated with culture-negative sepsis. Our nomogram, based on the MR-proADM levels, did not predict culture-negative status with reasonable certainty in patients with a definitive diagnosis of sepsis at ED admission

Genetic Variants of Matrix Metalloproteinase and Sepsis: The Need Speed Study

Many causal mechanisms in sepsis susceptibility are largely unknown and the functional genetic polymorphisms (GP) of matrix metalloproteinases (MMPs) and their natural tissue inhibitor of MMPs (TIMP1) could play a role in its development. GPs of MMPs and TIMP (namely MMP-1 rs1799750, MMP-3 rs3025058, MMP-8 rs11225395, MMP-9 rs2234681, and TIMP-1 rs4898) have been compared in 1058 patients with suspected sepsis to assess the association with susceptibility and etiology of sepsis. Prevalence of MMP8 rs11225395 G/G genotype was higher in sepsis patients than in those with non-infective Systemic Inflammatory Reaction Syndrome (35.6 vs. 26%, hazard ratio, HR 1.56, 95% C.I. 1.04–2.42, p = 0.032). G/G patients developed less hyperthermia (p = 0.041), even after stratification for disease severity (p = 0.003). Patients carrying the 6A allele in MMP3 rs3025058 had a higher probability of microbiologically-proven sepsis (HR 1.4. 95%C.I. 1.01–1.94, p = 0.044), particularly when due to virus (H.R. 2.14, 95% C.I. 1.06–4.31, p = 0.046), while MMP-1 G/G genotype patients carried a higher risk for intracellular bacteria (Chlamydia, Mycoplasma, and Legionella, H.R. 6.46, 95% C.I. 1.58–26.41, p = 0.003). Neither severity of sepsis at presentation, nor 30-day mortality were influenced by the investigated variants or their haplotype. MMP8 rs11225395 G/G carriers have lower temperature at presentation and a more than 50% increased susceptibility to sepsis. Among patients with sepsis, carriers of MMP1 rs1799750 G/G have an increased susceptibility for intracellular pathogen infections, while virus serology is more often positive in those with the MMP3 rs3025058 A/A genotype.</jats:p

Genetic Variants of Matrix Metalloproteinase and Sepsis: The Need Speed Study

Many causal mechanisms in sepsis susceptibility are largely unknown and the functional genetic polymorphisms (GP) of matrix metalloproteinases (MMPs) and their natural tissue inhibitor of MMPs (TIMP1) could play a role in its development. GPs of MMPs and TIMP (namely MMP-1 rs1799750, MMP-3 rs3025058, MMP-8 rs11225395, MMP-9 rs2234681, and TIMP-1 rs4898) have been compared in 1058 patients with suspected sepsis to assess the association with susceptibility and etiology of sepsis. Prevalence of MMP8 rs11225395 G/G genotype was higher in sepsis patients than in those with non-infective Systemic Inflammatory Reaction Syndrome (35.6 vs. 26%, hazard ratio, HR 1.56, 95% C.I. 1.04–2.42, p = 0.032). G/G patients developed less hyperthermia (p = 0.041), even after stratification for disease severity (p = 0.003). Patients carrying the 6A allele in MMP3 rs3025058 had a higher probability of microbiologically-proven sepsis (HR 1.4. 95%C.I. 1.01–1.94, p = 0.044), particularly when due to virus (H.R. 2.14, 95% C.I. 1.06–4.31, p = 0.046), while MMP-1 G/G genotype patients carried a higher risk for intracellular bacteria (Chlamydia, Mycoplasma, and Legionella, H.R. 6.46, 95% C.I. 1.58–26.41, p = 0.003). Neither severity of sepsis at presentation, nor 30-day mortality were influenced by the investigated variants or their haplotype. MMP8 rs11225395 G/G carriers have lower temperature at presentation and a more than 50% increased susceptibility to sepsis. Among patients with sepsis, carriers of MMP1 rs1799750 G/G have an increased susceptibility for intracellular pathogen infections, while virus serology is more often positive in those with the MMP3 rs3025058 A/A genotype

Are Baseline Levels of Gas6 and Soluble Mer Predictors of Mortality and Organ Damage in Patients with Sepsis? The Need-Speed Trial Database

Soluble tyrosine kinase receptor Mer (sMer) and its ligand Growth arrest-specific protein 6 (Gas6) are predictors of mortality in patients with sepsis. Our aim is to clarify whether their measurement at emergency department (ED) presentation is useful in risk stratification. We re-analyzed data from the Need-Speed trial, evaluating mortality and the presence of organ damage according to baseline levels of sMer and Gas6. 890 patients were eligible; no association with 7- and 30-day mortality was observed for both biomarkers (p &gt; 0.05). sMer and Gas6 levels were significantly higher in acute kidney injury (AKI) patients compared to non-AKI ones (9.8 [4.1–17.8] vs. 7.9 [3.8–12.9] ng/mL and 34.8 [26.4–47.5] vs. 29.8 [22.1–41.6] ng/mL, respectively, for sMer and Gas6), and Gas6 also emerged as an independent AKI predictor (odds ratio (OR) 1.01 [1.00–1.02]). Both sMer and Gas6 independently predicted thrombocytopenia in sepsis patients not treated with anticoagulants (OR 1.01 [1.00–1.02] and 1.04 [1.02–1.06], respectively). Moreover, sMer was an independent predictor of both prothrombin time-international normalized ratio (PT-INR) &gt; 1.4 (OR 1.03 [1.00–1.05]) and sepsis-induced coagulopathy (SIC) (OR 1.05 [1.02–1.07]). An early measurement of the sMer and Gas6 plasma concentration could not predict mortality. However, the biomarkers were associated with AKI, thrombocytopenia, PT-INR derangement and SIC, suggesting a role in predicting sepsis-related organ damage.</jats:p