scholarly journals Molecular RNA Correlates of the SOFA Score in Patients with Sepsis

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1649
Author(s):  
Agnes S. Meidert ◽  
Dominik Buschmann ◽  
Florian Brandes ◽  
Kristiyan Kanev ◽  
Jean-Noël Billaud ◽  
...  
Keyword(s):  
Sofa Score ◽  
Kidney Injury ◽  
Bioinformatic Analysis ◽  
Signaling Networks ◽  
Molecular Signaling ◽  
Reverse Transcription Pcr ◽  
Failure Assessment ◽  
Mrna Transcripts ◽  
Regulatory Functions ◽  
Independent Cohort

The most common scoring system for critically ill patients is the Sequential Organ Failure Assessment (SOFA) score. Little is known about specific molecular signaling networks underlying the SOFA criteria. We characterized these networks and identified specific key regulatory molecules. We prospectively studied seven patients with sepsis and six controls with high-throughput RNA sequencing (RNAseq). Quantitative reverse transcription PCR (RT-qPCR) confirmation was performed in a second independent cohort. Differentially and significantly expressed miRNAs and their target mRNA transcripts were filtered for admission SOFA criteria and marker RNAs for the respective criteria identified. We bioinformatically constructed molecular signaling networks specifically reflecting these criteria followed by RT-qPCR confirmation of RNAs with important regulatory functions in the networks in the second cohort. RNAseq identified 82 miRNAs (45% upregulated) and 3254 mRNAs (50% upregulated) differentially expressed between sepsis patients and controls. Bioinformatic analysis characterized 6 miRNAs and 76 mRNA target transcripts specific for the SOFA criteria. RT-qPCR validated miRNA and mRNAs included IGFBP2 (respiratory system); MMP9 and PDE4B (nervous system); PPARG (cardiovascular system); AKR1B1, ANXA1, and LNC2/NGAL (acute kidney injury); GFER/ALR (liver); and miR-30c-3p (coagulopathy). There are specific canonical networks underlying the SOFA score. Key regulatory miRNA and mRNA transcripts support its biologic validity.

scholarly journals Platelet-to-lymphocyte ratio as a prognostic predictor of mortality for sepsis: interaction effect with disease severity—a retrospective study

BMJ Open ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. e022896 ◽  
Author(s):  
Yanfei Shen ◽  
Xinmei Huang ◽  
Weimin Zhang
Keyword(s):  
Sofa Score ◽  
Logistic Model ◽  
Kidney Injury ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Failure Assessment ◽  
Vasopressor Use

ObjectiveThe role of platelet-to-lymphocyte ratio (PLR) as an indicator of inflammation has been the focus of research recently. We aimed to investigate theprognosticvalue of PLR for sepsis.DesignA retrospective cohort study.Setting and participantsData were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III database. Data on 5537 sepsis patients were analysed.MethodsLogistic regression was used to explore the association between PLR and hospital mortality. Subgroup analyses were performed based on vasopressor use, acute kidney injury (AKI) and a Sequential Organ Failure Assessment (SOFA) score >10.ResultsIn the logistic model with linear spline function, a PLR >200 was significantly (OR 1.0002; 95% CI 1.0001 to 1.0004) associated with mortality; the association wasnon-significantfor PLRs ≤200 (OR 0.997; 95% CI 1.19 to 1.67). In the logistic model using the PLR as a design variable, only high PLRs were significantly associated with mortality (OR 1.29; 95% CI 1.09 to 1.53); the association with low PLRs wasnon-significant(OR 1.15; 95% CI 0.96 to 1.38). In the subgroups with vasopressor use, AKI and a SOFA score >10, the association between high PLR and mortality wasnon-significant; this remained significant in the subgroups without vasopressor use (OR 1.39; 95% CI 1.08 to 1.77) and AKI (OR 1.54; 95% CI 1.20 to 1.99) and with a SOFA score ≤10 (OR 1.51; 95% CI 1.17 to 1.94).ConclusionsHigh PLRs at admission were associated with an increased risk of mortality. In patients with vasopressor use, AKI or a SOFA score >10, this association wasnon-significant.

scholarly journals Contribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Do Hyeon Cha ◽  
Heon Yung Gee ◽  
Raul Cachau ◽  
Jong Mun Choi ◽  
Daeui Park ◽  
...  
Keyword(s):  
Genetic Diagnosis ◽  
Kidney Injury ◽  
Genetic Identification ◽  
Diagnostic Screening ◽  
Renal Hypouricemia ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Causal Variants ◽  
Coding Variants ◽  
Independent Cohort

Abstract Differentiating between inherited renal hypouricemia and transient hypouricemic status is challenging. Here, we aimed to describe the genetic background of hypouricemia patients using whole-exome sequencing (WES) and assess the feasibility for genetic diagnosis using two founder variants in primary screening. We selected all cases (N = 31) with extreme hypouricemia (<1.3 mg/dl) from a Korean urban cohort of 179,381 subjects without underlying conditions. WES and corresponding downstream analyses were performed for the discovery of rare causal variants for hypouricemia. Two known recessive variants within SLC22A12 (p.Trp258*, pArg90His) were identified in 24 out of 31 subjects (77.4%). In an independent cohort, we identified 50 individuals with hypouricemia and genotyped the p.Trp258* and p.Arg90His variants; 47 of the 50 (94%) hypouricemia cases were explained by only two mutations. Four novel coding variants in SLC22A12, p.Asn136Lys, p.Thr225Lys, p.Arg284Gln, and p.Glu429Lys, were additionally identified. In silico studies predict these as pathogenic variants. This is the first study to show the value of genetic diagnostic screening for hypouricemia in the clinical setting. Screening of just two ethnic-specific variants (p.Trp258* and p.Arg90His) identified 87.7% (71/81) of Korean patients with monogenic hypouricemia. Early genetic identification of constitutive hypouricemia may prevent acute kidney injury by avoidance of dehydration and excessive exercise.

scholarly journals Establishment of a prognostic model based on the Sequential Organ Failure Assessment score for patients with first-time acute myocardial infarction

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110119
Author(s):  
Shuai Zheng ◽  
Jun Lyu ◽  
Didi Han ◽  
Fengshuo Xu ◽  
Chengzhuo Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Sequential Organ Failure Assessment ◽  
Organ Failure ◽  
Sofa Score ◽  
Cardiovascular Events ◽  
Failure Assessment ◽  
First Time

Objective This study aimed to identify the prognostic factors of patients with first-time acute myocardial infarction (AMI) and to establish a nomogram for prognostic modeling. Methods We studied 985 patients with first-time AMI using data from the Multi-parameter Intelligent Monitoring for Intensive Care database and extracted their demographic data. Cox proportional hazards regression was used to examine outcome-related variables. We also tested a new predictive model that includes the Sequential Organ Failure Assessment (SOFA) score and compared it with the SOFA-only model. Results An older age, higher SOFA score, and higher Acute Physiology III score were risk factors for the prognosis of AMI. The risk of further cardiovascular events was 1.54-fold higher in women than in men. Patients in the cardiac surgery intensive care unit had a better prognosis than those in the coronary heart disease intensive care unit. Pressurized drug use was a protective factor and the risk of further cardiovascular events was 1.36-fold higher in nonusers. Conclusion The prognosis of AMI is affected by age, the SOFA score, the Acute Physiology III score, sex, admission location, type of care unit, and vasopressin use. Our new predictive model for AMI has better performance than the SOFA model alone.

scholarly journals SOFA Score, Hemodynamics and Body Temperature Allow Early Discrimination between Porcine Peritonitis-Induced Sepsis and Peritonitis-Induced Septic Shock

2021 ◽  
Vol 11 (3) ◽  
pp. 164
Author(s):  
Mahmoud Al-Obeidallah ◽  
Dagmar Jarkovská ◽  
Lenka Valešová ◽  
Jan Horák ◽  
Jan Jedlička ◽  
...  
Keyword(s):  
Septic Shock ◽  
Body Temperature ◽  
Sofa Score ◽  
Porcine Model ◽  
Venous Blood ◽  
Mixed Venous Blood ◽  
Mechanically Ventilated ◽  
Multiple Parameters ◽  
Failure Assessment ◽  
Sepsis And Septic Shock

Porcine model of peritonitis-induced sepsis is a well-established clinically relevant model of human disease. Interindividual variability of the response often complicates the interpretation of findings. To better understand the biological basis of the disease variability, the progression of the disease was compared between animals with sepsis and septic shock. Peritonitis was induced by inoculation of autologous feces in fifteen anesthetized, mechanically ventilated and surgically instrumented pigs and continued for 24 h. Cardiovascular and biochemical parameters were collected at baseline (just before peritonitis induction), 12 h, 18 h and 24 h (end of the experiment) after induction of peritonitis. Analysis of multiple parameters revealed the earliest significant differences between sepsis and septic shock groups in the sequential organ failure assessment (SOFA) score, systemic vascular resistance, partial pressure of oxygen in mixed venous blood and body temperature. Other significant functional differences developed later in the course of the disease. The data indicate that SOFA score, hemodynamical parameters and body temperature discriminate early between sepsis and septic shock in a clinically relevant porcine model. Early pronounced alterations of these parameters may herald a progression of the disease toward irreversible septic shock.

scholarly journals 414. Association of SARS-CoV-2 Genomic Load Trends with Clinical Status in COVID-19:A Retrospective Analysis from an Academic Hospital Center in New York City

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S275-S275
Author(s):  
Ioannis Zacharioudakis ◽  
Fainareti Zervou ◽  
Prithiv Prasad ◽  
Yongzhao Shao ◽  
Atreyee Basu ◽  
...  
Keyword(s):  
New York ◽  
Sofa Score ◽  
Research Question ◽  
Clinical Status ◽  
Inverse Correlation ◽  
Duration Of Symptoms ◽  
Cycle Threshold ◽  
Ct Value ◽  
Failure Assessment ◽  
Polymerase Chain

Abstract Background The Infectious Diseases Society of America has identified the potential use of SARS-CoV-2 genomic load for prognostication purposes as a key research question. Methods We designed a retrospective cohort study that included adult patients with COVID-19 pneumonia who had at least 2 positive nasopharyngeal tests at least 24 hours apart to study the correlation between the change in the genomic load of SARS-CoV-2 in nasopharyngeal samples, as reflected by the Cycle threshold (Ct) value of the real-time Polymerase Chain Reaction (PCR) assay, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients’ clinical status. A linear mixed-effects regression analysis was performed. Results Among 457 patients who presented to the emergency department between 3/31/2020- 4/10/2020, we identified 42 patients who met the inclusion criteria. The median initial SOFA score was 2 (IQR 2–3). 20 out of 42 patients had a lower SOFA score on their subsequent tests. We identified a statistically significant inverse correlation between the change in SOFA score and change in the Ct value with a decrease in SOFA score by 0.05 (SE 0.02; p &lt; 0.05) for an increase in Ct values by 1. This correlation was independent of the duration of symptoms. Flow chart A graph of the Cycle Threshold (Ct) values of the of Cepheid Xpert® Xpress SARS-CoV-2 assay measured on repeat screening of the 42 included patients. Graph of the fitted SOFA scores based on the Cycle Threshold values per patient. Conclusion Our findings suggest that an increasing Ct value in sequential tests may be of prognostic value for patients diagnosed with COVID-19 pneumonia. Before repeat testing can be recommended routinely in clinical practice as a predictor of disease outcomes, prospective studies with a standardized interval between repeat tests should confirm our findings. Disclosures All Authors: No reported disclosures

scholarly journals Identification of anticancer drug target genes using an outside competitive dynamics model on cancer signaling networks

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tien-Dzung Tran ◽  
Duc-Tinh Pham
Keyword(s):  
Anticancer Drug ◽  
Drug Target ◽  
Target Genes ◽  
Signaling Network ◽  
Competitive Dynamics ◽  
Signaling Networks ◽  
Molecular Signaling ◽  
Dynamics Model ◽  
Cancer Signaling ◽  
The Impact

AbstractEach cancer type has its own molecular signaling network. Analyzing the dynamics of molecular signaling networks can provide useful information for identifying drug target genes. In the present study, we consider an on-network dynamics model—the outside competitive dynamics model—wherein an inside leader and an opponent competitor outside the system have fixed and different states, and each normal agent adjusts its state according to a distributed consensus protocol. If any normal agent links to the external competitor, the state of each normal agent will converge to a stable value, indicating support to the leader against the impact of the competitor. We determined the total support of normal agents to each leader in various networks and observed that the total support correlates with hierarchical closeness, which identifies biomarker genes in a cancer signaling network. Of note, by experimenting on 17 cancer signaling networks from the KEGG database, we observed that 82% of the genes among the top 3 agents with the highest total support are anticancer drug target genes. This result outperforms those of four previous prediction methods of common cancer drug targets. Our study indicates that driver agents with high support from the other agents against the impact of the external opponent agent are most likely to be anticancer drug target genes.

scholarly journals Early Changes in the Sequential Organ Failure Assessment Score Among Patients With Sepsis-Induced Disseminated Intravascular Coagulation

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 332S-339S
Author(s):  
Katsunori Mochizuki ◽  
Kotaro Mori ◽  
Yuta Nakamura ◽  
Ryo Uchimido ◽  
Hiroshi Kamijo ◽  
...  
Keyword(s):  
Infection Control ◽  
Sequential Organ Failure Assessment ◽  
Organ Failure ◽  
Disseminated Intravascular Coagulation ◽  
Sofa Score ◽  
Early Improvement ◽  
Initial Infection ◽  
Soluble Thrombomodulin ◽  
Failure Assessment ◽  
Recombinant Human Soluble Thrombomodulin

It is unclear whether initial infection control or anticoagulant therapy exerts a greater effect on early changes in the Sequential Organ Failure Assessment (SOFA) score among patients with sepsis-induced disseminated intravascular coagulation (DIC). This retrospective propensity score cohort study aimed to evaluate whether adequacy of infection control or anticoagulation therapy had a greater effect on early changes in the SOFA scores among 52 patients with sepsis-induced DIC. Inadequate initial infection control was associated with a lower 28-day survival rate among patients with sepsis-induced DIC (odds ratio [OR]: 0.116, 95% confidence interval [CI]: 0.022-0.601; P = .010); however, the adequacy was not associated with an early improvement in the SOFA score. However, despite adjusting for inadequate initial infection control, administration of recombinant human soluble thrombomodulin was associated with an early improvement in the SOFA score (OR: 5.058, 95% CI: 1.047-24.450; P = .044). Therefore, early changes in the SOFA score within 48 hours after the DIC diagnosis were more strongly affected by the administration of recombinant human soluble thrombomodulin than the adequacy of initial infection control.

Sign in / Sign up

Export Citation Format

Share Document