scholarly journals Regulation and Prognostic Relevance of Symmetric Dimethylarginine Serum Concentrations in Critical Illness and Sepsis

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Alexander Koch ◽  
Ralf Weiskirchen ◽  
Jan Bruensing ◽  
Hanna Dückers ◽  
Lukas Buendgens ◽  
...  
Keyword(s):  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Multiorgan Failure ◽  
Microvascular Dysfunction ◽  
Serum Levels ◽  
Serum Concentrations ◽  
Symmetric Dimethylarginine ◽  
Term Survival ◽  
Severity Scores

In systemic inflammation and sepsis, endothelial activation and microvascular dysfunction are characteristic features that promote multiorgan failure. As symmetric dimethylarginine (SDMA) impacts vascular tension and integrity via modulating nitric oxide (NO) pathways, we investigated circulating SDMA in critical illness and sepsis. 247 critically ill patients (160 with sepsis, 87 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU) and on day 7, in comparison to 84 healthy controls. SDMA serum levels were significantly elevated in critically ill patients at admission to ICU compared to controls and remained stably elevated during the first week of ICU treatment. The highest SDMA levels were found in patients with sepsis. SDMA levels closely correlated with disease severity scores, biomarkers of inflammation, and organ failure (renal, hepatic, and circulatory). We identified SDMA serum concentrations at admission as an independent prognostic biomarker in critically ill patients not only for short-term mortality at the ICU but also for unfavourable long-term survival. Thus, the significant increase of circulating SDMA in critically ill patients indicates a potential pathogenic involvement in endothelial dysfunction during sepsis and may be useful for mortality risk stratification at the ICU.

scholarly journals Elevated Omentin Serum Levels Predict Long-Term Survival in Critically Ill Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Mark Luedde ◽  
Fabian Benz ◽  
Jennifer Niedeggen ◽  
Mihael Vucur ◽  
Hans-Joerg Hippe ◽  
...  
Keyword(s):  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Serum Levels ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
Term Survival ◽  
Icu Patients ◽  
Icu Treatment

Introduction. Omentin, a recently described adipokine, was shown to be involved in the pathophysiology of inflammatory and infectious diseases. However, its role in critical illness and sepsis is currently unknown. Materials and Methods. Omentin serum concentrations were measured in 117 ICU-patients (84 with septic and 33 with nonseptic disease etiology) admitted to the medical ICU. Results were compared with 50 healthy controls. Results. Omentin serum levels of critically ill patients at admission to the ICU or after 72 hours of ICU treatment were similar compared to healthy controls. Moreover, circulating omentin levels were independent of sepsis and etiology of critical illness. Notably, serum concentrations of omentin could not be linked to concentrations of inflammatory cytokines or routinely used sepsis markers. While serum levels of omentin were not predictive for short term survival during ICU treatment, low omentin concentrations were an independent predictor of patients’ overall survival. Omentin levels strongly correlated with that of other adipokines (e.g., leptin receptor or adiponectin), which have also been identified as prognostic markers in critical illness. Conclusions. Although circulating omentin levels did not differ between ICU-patients and controls, elevated omentin levels were predictive for an impaired patients’ long term survival.

scholarly journals Low Myostatin Serum Levels Are Associated with Poor Outcome in Critically Ill Patients

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 574
Author(s):  
Theresa H. Wirtz ◽  
Sven H. Loosen ◽  
Lukas Buendgens ◽  
Berkan Kurt ◽  
Samira Abu Jhaisha ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Cox Regression ◽  
Muscle Growth ◽  
Serum Levels ◽  
Serum Concentrations ◽  
Icu Patients ◽  
Cox Regression Analysis ◽  
Independent Prognostic Marker ◽  
Unfavorable Clinical Outcome

Background: Growth differentiation factor 8, GDF-8 (Myostatin), is a protein released by myocytes inhibiting muscle growth and differentiation. Serum concentrations of Myostatin can predict poor survival in different chronic diseases, but its role in critical illness and sepsis is obscure. Our aim was to investigate Myostatin levels as a potential prognostic biomarker in critically ill patients with sepsis. Methods: We therefore measured Myostatin serum concentrations in 165 critically ill patients (106 with sepsis, 59 without sepsis) upon admission to the medical intensive care unit (ICU), in comparison to 14 healthy controls. Results: Myostatin levels were significantly decreased in ICU patients compared to controls but did not differ in patients with or without sepsis. However, Myostatin concentrations were significantly lower in patients requiring mechanical ventilation and indicated a trend towards dependency of intravenous vasopressors. Interestingly, we observed a negative correlation between Myostatin levels and markers of systemic inflammation. Strikingly, overall survival (OS) was significantly impaired in patients with low Myostatin levels in all critically ill patients. Low Myostatin levels at baseline turned out as an independent prognostic marker for OS in multivariate Cox-regression analysis (HR: 0.433, 95% CI: 0.211–0.889, p = 0.023). Conclusions: In summary, serum Myostatin concentrations are significantly decreased in critically ill patients and associated with disease severity. Low Myostatin levels also identify a subgroup of ICU patients that are more likely to face an unfavorable clinical outcome in terms of OS.

scholarly journals miR-155 Predicts Long-Term Mortality in Critically Ill Patients Younger than 65 Years

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Frank Tacke ◽  
Martina E. Spehlmann ◽  
Mihael Vucur ◽  
Fabian Benz ◽  
Mark Luedde ◽  
...  
Keyword(s):  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Prognostic Biomarker ◽  
Serum Levels ◽  
Disease Etiology ◽  
Age Related ◽  
Age Dependent ◽  
Similar Accuracy

Introduction. Alterations in miR-155 serum levels have been described in inflammatory and infectious diseases. Moreover, a role for miR-155 in aging and age-related diseases was recently suggested. We therefore analyzed a potential age-dependent prognostic value of circulating miR-155 as a serum-based marker in critical illness. Methods. Concentrations of circulating miR-155 were determined in 218 critically ill patients and 76 healthy controls. Results. By using qPCR, we demonstrate that miR-155 serum levels are elevated in patients with critical illness when compared to controls. Notably, levels of circulating miR-155 were independent on the severity of disease, the disease etiology, or the presence of sepsis. In the total cohort, miR-155 was not an indicator for patient survival. Intriguingly, when patients were subdivided according to their age upon admission to the ICU into those younger than 65 years, lower levels of miR-155 turned out as a strong marker, indicating patient mortality with a similar accuracy than other markers frequently used to evaluate critically ill patients on a medical ICU. Conclusion. In summary, the data provided within this study suggest an age-specific role of miR-155 as a prognostic biomarker in patients younger than 65 years. Our study is the first to describe an age-dependent miRNA-based prognostic biomarker in human diseases.

Cytokines in Chronically Critically Ill Patients After Activity and Rest

2007 ◽  
Vol 8 (4) ◽  
pp. 261-271 ◽  
Author(s):  
Chris Winkelman ◽  
Patricia A. Higgins ◽  
Yea Jyh Kathy Chen ◽  
Alan D. Levine
Keyword(s):  
Physical Activity ◽  
Mechanical Ventilation ◽  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Prolonged Mechanical Ventilation ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Chronically Critically Ill ◽  
Critically Ill Adults

Inflammation, a common problem for patients in the intensive care unit (ICU), frequently is associated with serious and prolonged critical illnesses. To date, no study has examined whether physical activity influences inflammatory factors in critically ill adults. The objectives of this study were to (a) examine the relationships between type and duration of physical activity and serum levels of interleukin 6 (IL-6), a proinflammatory cytokine; IL-10, an anti-inflammatory cytokine; and their ratio and (b) determine if there are associations between cytokines or their ratio and activity or outcomes. This descriptive feasibility study investigated the approaches to measuring levels of physical activity and its relationship to serum levels of IL-6 and IL-10 and the ratio between them in patients with prolonged mechanical ventilation during periods of activity and rest. Measurements included serum IL-6 and IL-10 levels, direct observation and actigraphy, and prospective chart review. Ten critically ill patients who were mechanically ventilated for an average of 10 days in a large, urban, teaching hospital were enrolled. The average ratio of IL-6 to IL-10 improved after an average of 14.7 min of passive physical activity, typically multiple in-bed turns associated with hygiene. IL-6, IL-10, and their ratio were not associated with patient outcomes of weaning success or length of stay. High levels of IL-6 were associated with mortality. Cytokine balance may be improved by low levels of activity among patients with prolonged critical illness. The pattern of cytokines produced after activity may improve patients' recovery from prolonged critical illness and mechanical ventilation.

scholarly journals Circulating MicroRNA-223 Serum Levels Do Not Predict Sepsis or Survival in Patients with Critical Illness

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Fabian Benz ◽  
Frank Tacke ◽  
Mark Luedde ◽  
Christian Trautwein ◽  
Tom Luedde ◽  
...  
Keyword(s):  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Inflammatory Responses ◽  
Elevated Serum ◽  
Serum Levels ◽  
Apache Ii Score ◽  
Circulating Microrna ◽  
Icu Patients ◽  
Markers Of Inflammation

Background and Aims. Dysregulation of miR-223 was recently linked to various diseases associated with systemic inflammatory responses such as type 2 diabetes, cancer, and bacterial infections. However, contradictory results are available on potential alterations of miR-223 serum levels during sepsis. We thus aimed to evaluate the diagnostic and prognostic value of miR-223 serum concentrations in patients with critical illness and sepsis.Methods. We used i.v. injection of lipopolysaccharide (LPS) as well as cecal pole ligation and puncture (CLP) for induction of polymicrobial sepsis in mice and measured alterations in serum levels of miR-223. These results from mice were translated into a large and well-characterized cohort of critically ill patients admitted to the medical intensive care unit (ICU). Finally, results from analysis in patients were correlated with clinical data and extensive sets of routine and experimental biomarkers.Results. Although LPS injection induced moderately elevated serum miR-223 levels in mice, no significant alterations in miR-223 serum levels were found in mice after CLP-induced sepsis. In accordance with these results from animal models, serum miR-223 levels did not differ between critically ill patients and healthy controls. However, ICU patients with more severe disease (APACHE-II score) showed moderately reduced circulating miR-223. Strikingly, no differences in miR-223 levels were found in critically ill patients with or without sepsis, and serum levels of miR-223 did not correlate with classical markers of inflammation or bacterial infection. Finally, low miR-223 serum levels were moderately associated with an unfavorable prognosis of patients during the ICU treatment but did not predict long-term mortality.Conclusion. Recent reports on alterations in miR-223 serum levels during sepsis revealed contradictory results, preventing a potential use of this miRNA in clinical routine. We clearly show that miR-223 serum levels do not reflect the presence of sepsis neither in mouse models nor in a large cohort of ICU patients and do not indicate clinical outcome of critically ill patients. Thus miR-223 serum levels should not be used as a biomarker in this setting.

scholarly journals Midregional Proadrenomedullin (MRproADM) Serum Levels in Critically Ill Patients Are Associated with Short-Term and Overall Mortality during a Two-Year Follow-Up

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Lukas Buendgens ◽  
Eray Yagmur ◽  
Axel Ginsberg ◽  
Ralf Weiskirchen ◽  
Theresa Wirtz ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Prognostic Biomarker ◽  
Serum Levels ◽  
Diagnostic Value ◽  
Healthy Controls ◽  
Icu Mortality ◽  
Term Survival ◽  
Overall Mortality

Adrenomedullin (ADM) is a peptide with pleiotropic effects in systemic inflammation. Its more stable precursor protein midregional proadrenomedullin (MRproADM) can be measured more reliably compared to ADM. Our objective was to investigate the potential role of MRproADM as a diagnostic and prognostic biomarker in critically ill patients at the intensive care unit (ICU). We therefore measured MRproADM in 203 ICU patients and 66 healthy controls. We found that MRproADM levels are significantly increased in critically ill patients as compared to healthy controls. MRproADM levels are significantly increased in patients with sepsis, but its diagnostic value for identifying sepsis is numerically lower than that of established markers (e.g., interleukin-6, C-reactive protein, and procalcitonin). MRproADM levels are closely correlated to endothelial and organ dysfunction, inflammation, and established clinical scores (APACHE II, SOFA, and SAPS2). MRproADM concentrations correlate with vasopressor use but not fluid balance. Increased MRproADM levels (cut−off>1.4 nmol/L) in critically ill patients are independent predictors of ICU and overall mortality during a follow-up of up to 26 months (OR 3.15 for ICU mortality, 95% CI 1.08-9.20, p=0.036; OR for overall mortality 2.4, 95% CI 1.12-5.34, p=0.026). Our study demonstrates the potential of MRproADM serum levels as a prognostic biomarker in critical illness for ICU mortality and long-term survival during follow-up.

Angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism and circulating ACE levels are not associated with outcome in critically ill septic patients

2012 ◽  
Vol 50 (2) ◽  
Author(s):  
Argirios Tsantes ◽  
Iraklis Tsangaris ◽  
Petros Kopterides ◽  
Georgios Nikolopoulos ◽  
Eleni Kalamara ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Clinical Outcomes ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Prognostic Significance ◽  
Serum Levels ◽  
Converting Enzyme ◽  
Ace Polymorphism ◽  
Cardiovascular Failure ◽  
Severity Scores

AbstractIn critically ill patients independent studies have shown contradictory findings regarding the prognostic significance of the D/D genotype of the I/D angiotensin converting enzyme (ACE) polymorphism. The study aim was to evaluate the effect of both ACE I/D polymorphism and ACE serum levels on the clinical outcomes of critically ill septic patients.This study recruited 186 Caucasian patients with sepsis, severe sepsis or septic shock. Epidemiological, clinical data, co-morbidities and severity scores were recorded. Measurements of serum ACE activity and genotyping for ACE I/D polymorphism were carried out. Primary outcomes were the 28- and the 90-day mortality; secondary outcomes included the number of days without renal or cardiovascular failure and ventilation-free days over the 28-day period following study enrolment.Neither 28- nor 90-day mortality were associated with ACE I/D polymorphism (p=0.59 and 0.34, respectively) or circulating ACE levels (p=0.17 and 0.25, respectively). Similarly, ACE polymorphism and levels were not related to ventilation-free days (p=0.14 and 0.25, respectively), days without cardiovascular failure (p=0.14 and 0.81, respectively) and days without renal failure (p=0.64 and 0.27, respectively).Neither ACE I/D polymorphism nor serum ACE levels seem to be significant prognostic factors of clinical outcomes in septic, critically ill patients.

scholarly journals Low Serum Levels of Soluble Receptor Activator of Nuclear Factor κ B Ligand (sRANKL) Are Associated with Metabolic Dysregulation and Predict Long-Term Mortality in Critically Ill Patients

Diagnostics ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 62
Author(s):  
Tobias Puengel ◽  
Beate Weber ◽  
Theresa H. Wirtz ◽  
Lukas Buendgens ◽  
Sven H. Loosen ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Serum Levels ◽  
Nuclear Factor ◽  
Soluble Receptor ◽  
Serum Concentrations ◽  
Icu Admission ◽  
Metabolic Dysregulation ◽  
Receptor Activator ◽  
Nuclear Factor Κ B

Soluble receptor activator of nuclear factor κ B ligand (sRANKL) is a member of the tumor necrosis factor receptor superfamily, and therefore, involved in various inflammatory processes. The role of sRANKL in the course of bone remodeling via activation of osteoclasts as well as chronic disease progression has been described extensively. However, the potential functional importance of sRANKL in critically ill or septic patients remained unknown. Therefore, we measured sRANKL serum concentrations in 303 critically ill patients, including 203 patients with sepsis and 100 with non-sepsis critical illness. Results were compared to 99 healthy controls. Strikingly, in critically ill patients sRANKL serum levels were significantly decreased at intensive care unit (ICU) admission (p = 0.011) without differences between sepsis and non-sepsis patients. Inline, sRANKL was correlated with markers of metabolic dysregulation, such as pre-existing diabetes and various adipokines (e.g., adiponectin, leptin receptor). Importantly, overall mortality of critically ill patients in a three-year follow-up was significantly associated with decreased sRANKL serum concentrations at ICU admission (p = 0.038). Therefore, our study suggests sRANKL as a biomarker in critically ill patients which is associated with poor prognosis and overall survival beyond ICU stay.

scholarly journals Vitamin D serum levels in multiorgan failure critically ill patients undergoing continuous renal replacement therapies

2020 ◽  
Vol 52 (5) ◽  
pp. 359-365
Author(s):  
Tomasz Czarnik ◽  
Aneta Czarnik ◽  
Ryszard Gawda ◽  
Maciej Piwoda ◽  
Maciej Marszalski ◽  
...  
Keyword(s):  
Vitamin D ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Multiorgan Failure ◽  
Serum Levels ◽  
Renal Replacement Therapies ◽  
Continuous Renal Replacement Therapies

Critical Illness Outcomes Study: An Observational Cohort Of Critically Ill Patients

2012 ◽  
Author(s):  
Jonathan E. Sevransky ◽  
William Checkley ◽  
Timothy D. Girard ◽  
Steven M. Pastores ◽  
Sajid Shahul ◽  
...  
Keyword(s):  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Observational Cohort ◽  
Outcomes Study ◽  
Illness Outcomes
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