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 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 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 Methadone Pharmacokinetics in Geriatric Critically Ill Patients Following Intramuscular and Intravenous Administration: A Pilot Stud

2020 ◽  
Author(s):  
Safoura Beik Rassouli ◽  
Mohammad Reza Rouini ◽  
Farhad Najmeddin ◽  
Azin Gheimati ◽  
Ali A Golabchifar ◽  
...  
Keyword(s):  
Pain Management ◽  
Critically Ill ◽  
Intravenous Administration ◽  
Critically Ill Patients ◽  
Half Life ◽  
Serum Levels ◽  
Volume Of Distribution ◽  
Icu Patients ◽  
Potential Alternative ◽  
Pharmacokinetic Behavior

Background: Methadone is used for the pain management worldwide. Its special characteristics make it a potential alternative for pain management in critically ill and geriatric patients. Due to lack of studies in this population, we aimed to compare the pharmacokinetic behavior of Methadone following intramuscular and intravenous administration in geriatric ICU patients and with previously reports in healthy volunteers. Methods: According to the limitations in ICU setting, we could include 11 patients over 65 years old, who required opioid for pain relief in this study. Patients were randomized to receive 5 mg of Methadone IM or IV injection every 8 hours for 6 days. The Methadone plasma level detected with LC-mass tandem mass spectrometry, and pharmacokinetics parameters were evaluated for each subject in both 1st and 6th days of treatment. Results: Based on our results, bioavailability of intramuscular Methadone in geriatric ICU patients was low and less than 40% of the dose was absorbed within first 12 hours. The volume of distribution of Methadone in the first day was significantly lower than the previously reported values in healthy subjects and significantly increased during these 6 days. The Methadone half-life in this population also significantly increased through this period. Conclusion: Pharmacokinetic behavior of Methadone in geriatric ICU patients is unpredictable. Reduced volume of distribution and half-life may be observed initially, following with an increase to the normal range. It seems that IM administration of Methadone in geriatric critically ill patients may not provide target analgesic Methadone serum levels.

scholarly journals Whether Early Pulse Steroid dose is associated with lower mortality in COVID-19 critically ill Patients- An exploratory retrospective Chart Review

2020 ◽  
Author(s):  
Abhishek Goyal ◽  
Saurabh Saigal ◽  
Ankur Joshi ◽  
Dodda Brahmam ◽  
Yogesh Niwariya ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Protective Effect ◽  
Critically Ill ◽  
Steroid Therapy ◽  
Critically Ill Patients ◽  
Chart Review ◽  
Cox Regression ◽  
Exploratory Analysis ◽  
Model Diagnostics ◽  
Cox Regression Analysis

Introduction: Steroids have shown its usefulness in critically ill COVID19 patients. However time of starting steroid and dose tailored to severity remains a matter of inquiry due to still emerging evidences and wide-ranging concerns of benefits and harms. We did a retrospective record analysis in an apex teaching hospital ICU setting to explore optimal doses and duration of steroid therapy which minimizes the hazard of death. Methodology: 114 adults with COVID19-ARDS admitted to ICU between 20thMarch-15thAugust2020 were included in chart review. We did preliminary exploratory analysis(rooted in steroid therapy matrix categorized by dose and duration) to understand the effect of several covariates on survival. This was followed by univariate and multivariate Cox proportion hazard regression analysis and model diagnostics. Results: Exploratory analysis and visualization indicated age, optimal steroid, severity (measured in P/F) of disease and infection status as potential covariates for survival. Univariate cox regression analysis showed significant positive association of age>60 years{2.6 (1.5-4.7)} and protective effect of optimum steroid{0.38(0.2-0.72)} on death (hazard) in critically ill patients. Multivariate cox regression analysis after adjusting effect of age showed protective effect of optimum steroid on hazard defined as death {0.46(0.23-0.87),LR=17.04,(p=2e-04)}.The concordance was 0.70 and model diagnostics fulfilled the assumption criteria for proportional hazard model. Conclusion: Optimal dose steroid as per defined optimum(<24 hours and doses tailored to P/F at presentation) criteria can offer protective effect from mortality which persists after adjusting for age. This protective effect was not found to be negatively influenced by the risk of infection.

scholarly journals High Circulating Caspase-Cleaved Keratin 18 Fragments (M30) Indicate Short-Term Mortality in Critically Ill Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Alexander Koch ◽  
Eray Yagmur ◽  
Janine Linka ◽  
Fabienne Schumacher ◽  
Jan Bruensing ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Cell Injury ◽  
Serum Levels ◽  
Intermediate Filament Protein ◽  
Healthy Controls ◽  
Short Term ◽  
Icu Patients ◽  
Short Term Mortality ◽  
Keratin 18

Caspase-cleaved fragments of the intermediate filament protein keratin 18 (cytokeratin-18 (CK18)) can be detected in serum as M30 levels and may serve as a circulating biomarker indicating apoptosis of epithelial and parenchymal cells. In order to evaluate M30 as a biomarker in critical illness, we analyzed circulating M30 levels in 243 critically ill patients (156 with sepsis, 87 without sepsis) at admission to the medical intensive care unit (ICU), in comparison to healthy controls (n=32). M30 levels were significantly elevated in ICU patients compared with healthy controls. Circulating M30 was closely associated with disease severity but did not differ between patients with sepsis and ICU patients without sepsis. M30 serum levels were correlated with biomarkers of inflammation, cell injury, renal failure, and liver failure in critically ill patients. Patients that died at the ICU showed increased M30 levels at admission, compared with surviving patients. A similar trend was observed for the overall survival. Regression analyses confirmed that M30 levels are associated with mortality, and patients with M30 levels above 250.8 U/L displayed an excessive short-term mortality. Thus, our data support the utility of circulating levels of the apoptosis-related keratin fragment M30 as a prognostic biomarker at ICU admission.

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 Does Antimicrobial Therapy Affect Mortality of Patients with Carbapenem-Resistant Klebsiella pneumoniae Bacteriuria? A Nationwide Multicenter Study in Taiwan

2020 ◽  
Vol 8 (12) ◽  
pp. 2035
Author(s):  
Chien Chuang ◽  
Chin-Fang Su ◽  
Jung-Chung Lin ◽  
Po-Liang Lu ◽  
Ching-Tai Huang ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Klebsiella Pneumoniae ◽  
Critically Ill ◽  
Antimicrobial Therapy ◽  
Critically Ill Patients ◽  
Cox Regression ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Cox Regression Analysis ◽  
Carbapenem Resistant

Few clinical studies have previously discussed patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteriuria. This study aimed to assess the effect of antimicrobial therapy on the mortality of patients with CRKP bacteriuria. Hospitalized adults with CRKP bacteriuria were enrolled retrospectively from 16 hospitals in Taiwan during 2013 and 2014. Critically ill patients were defined as those with an Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥ 20. Multivariate Cox regression analysis was used to determine independent risk factors for 14- and 28-day mortality. Of 107 patients with CRKP bacteriuria, the 14-day and 28-day mortality was 14.0% and 25.2%, respectively. Thirty-three patients received appropriate antimicrobial therapy. In the multivariate Cox regression analysis, the APACHE II score ≥ 20 was the only independent risk factor for 14-day mortality (hazard ratio [HR]: 6.15, p = 0.024). APACHE II score ≥ 20 (HR: 3.05, p = 0.018) and male sex (HR: 2.57, p = 0.037) were associated with 28-day mortality. Among critically ill patients with CRKP bacteriuria, appropriate antimicrobial therapy was not associated with 14-day or 28-day survival. In conclusion, in patients with CRKP bacteriuria, the use of appropriate antimicrobial therapy was not an independent factor associated with reduced mortality. Our findings may inform future antibiotic stewardship interventions for bacteriuria caused by multidrug resistant pathogens.

scholarly journals The repurposed use of anesthesia machines to ventilate critically ill patients with coronavirus disease 2019 (COVID-19)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maurizio Bottiroli ◽  
Angelo Calini ◽  
Riccardo Pinciroli ◽  
Ariel Mueller ◽  
Antonio Siragusa ◽  
...  
Keyword(s):  
Critical Care ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Cox Regression ◽  
Northern Italy ◽  
Mechanical Ventilators ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Increased Risk ◽  
Anesthesia Machines

Abstract Background The surge of critically ill patients due to the coronavirus disease-2019 (COVID-19) overwhelmed critical care capacity in areas of northern Italy. Anesthesia machines have been used as alternatives to traditional ICU mechanical ventilators. However, the outcomes for patients with COVID-19 respiratory failure cared for with Anesthesia Machines is currently unknow. We hypothesized that COVID-19 patients receiving care with Anesthesia Machines would have worse outcomes compared to standard practice. Methods We designed a retrospective study of patients admitted with a confirmed COVID-19 diagnosis at a large tertiary urban hospital in northern Italy. Two care units were included: a 27-bed standard ICU and a 15-bed temporary unit emergently opened in an operating room setting. Intubated patients assigned to Anesthesia Machines (AM group) were compared to a control cohort treated with standard mechanical ventilators (ICU-VENT group). Outcomes were assessed at 60-day follow-up. A multivariable Cox regression analysis of risk factors between survivors and non-survivors was conducted to determine the adjusted risk of death for patients assigned to AM group. Results Complete daily data from 89 mechanically ventilated patients consecutively admitted to the two units were analyzed. Seventeen patients were included in the AM group, whereas 72 were in the ICU-VENT group. Disease severity and intensity of treatment were comparable between the two groups. The 60-day mortality was significantly higher in the AM group compared to the ICU-vent group (12/17 vs. 27/72, 70.6% vs. 37.5%, respectively, p = 0.016). Allocation to AM group was associated with a significantly increased risk of death after adjusting for covariates (HR 4.05, 95% CI: 1.75–9.33, p = 0.001). Several incidents and complications were reported with Anesthesia Machine care, raising safety concerns. Conclusions Our results support the hypothesis that care associated with the use of Anesthesia Machines is inadequate to provide long-term critical care to patients with COVID-19. Added safety risks must be considered if no other option is available to treat severely ill patients during the ongoing pandemic. Clinical trial number Not applicable.

Higher versus Lower Continuous Renal Replacement Therapy Intensity in Critically ill Patients with Liver Dysfunction

2017 ◽  
Vol 45 (1-3) ◽  
pp. 36-43 ◽  
Author(s):  
Zachary O'Brien ◽  
Alan Cass ◽  
Louise Cole ◽  
Simon Finfer ◽  
Martin Gallagher ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Liver Dysfunction ◽  
Critically Ill Patients ◽  
Cox Regression ◽  
Lower Intensity ◽  
Cox Regression Analysis ◽  
Lower Continuous

Aims: To study the association between higher versus lower continuous renal replacement therapy (CRRT) intensity and mortality in critically ill patients with combined acute kidney injury and liver dysfunction. Methods: Post-hoc analysis of patients with liver dysfunction (Sequential Organ Failure Assessment liver score ≥2 or diagnosis of liver failure/transplant) included in the Randomized Evaluation of Normal versus Augmented Level renal replacement therapy (RENAL) trial. Results: Of 444 patients, 210 (47.3%) were randomized to higher intensity (effluent flow 40 mL/kg/h) and 234 (52.7%) to lower intensity (effluent flow 25 mL/kg/h) therapy. Overall, 79 and 86% of prescribed effluent flow was delivered in the higher-intensity and lower-intensity groups, respectively (p < 0.001). In total, 113 (54.1%) and 120 (51.3%) patients died in each group. On multivariable Cox regression analysis, we found no independent association between higher CRRT intensity and mortality (HR 0.93, 95% CI 0.70-1.24; p = 0.642). Conclusions: In RENAL patients with liver dysfunction, higher CRRT intensity was not associated with reduced mortality.

scholarly journals Albumin–Globulin Ratio Is an Independent Determinant of 28-Day Mortality in Patients with Critical Illness

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Bin Liu ◽  
Kun Xiao ◽  
Peng Yan ◽  
Tianyu Sun ◽  
Jiang Wang ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Cox Regression ◽  
Independent Predictor ◽  
Laboratory Data ◽  
Cox Regression Analysis ◽  
Increased Risk

Background. Critical illness in the intensive care unit (ICU) has been a global health priority. Systemic nutritional status has turned out to be related to the prognosis of critically ill patients. The albumin-globulin ratio (AGR) has been reported to be a novel prognostic factor of many diseases. This study is aimed at investigating whether the AGR could predict the mortality risk in critically ill patients. Methods. We enrolled 582 adult patients admitted to the respiratory intensive care unit (RICU). We collected the clinical and laboratory data. X-tile software was used to determine the optimal cut-off values for the AGR. Patients were divided into three groups according to the AGR (low AGR group with AGR < 0.8 , medium AGR group with AGR ranging from 0.8 to 1.1, and high AGR group with AGR > 1.1 ). Kaplan-Meier analysis was used for survival analysis. A Cox proportional hazard model was applied to the univariate and multivariate analyses for the potential predictors associated with survival. Results. Our present study showed that the AGR was related to the 28-day survival of critically ill patients in the RICU. The rate of pneumonia in the low AGR group was significantly higher than that in the other groups. Patients with a lower AGR present an increased risk of 28-day mortality compared to patients with a higher AGR. Cox regression analysis showed that the AGR might be an independent predictor of prognosis to 28-day survival in critically ill patients in the RICU. Medium and high AGR values remained independently associated with better 28-day survival than low AGR values (HR: 0.484 (0.263-0.892) ( p = 0.02 ); HR: 0.332 (0.166-0.665) ( p = 0.002 )). Conclusion. The AGR might be an independent predictor of prognosis in critically ill patients.

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