scholarly journals The Activin/Follistatin-axis is severely deregulated in COVID-19 and independently associated with in-hospital mortality

2020 ◽  
Author(s):  
Evgenia Synolaki ◽  
Vasileios Papadopoulos ◽  
Georgios Divolis ◽  
Olga Tsahouridou ◽  
Efstratios Gavriilidis ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Fatal Outcome ◽  
Clinical Decision ◽  
Activin A ◽  
Serum Samples ◽  
Dynamic Prediction ◽  
Neutrophil Lymphocyte Ratio ◽  
Over Expression ◽  
Initial Cohort ◽  
Natural Inhibitor

AbstractBackgroundActivins are members of the TGFβ-superfamily implicated in the pathogenesis of several immuno-inflammatory disorders. Based on our previous studies demonstrating that over-expression of Activin-A in murine lung causes pathology sharing key features of COVID-19, we hypothesized that Activins and their natural inhibitor Follistatin might be particularly relevant to COVID-19 pathophysiology.MethodsActivin-A, Activin-B and Follistatin levels were retrospectively analyzed in 574 serum samples from 263 COVID-19 patients hospitalized in three independent centers, and compared with common demographic, clinical and laboratory parameters. Optimal-scaling with ridge-regression was used to screen variables and establish a prediction model.ResultThe Activin/Follistatin-axis was significantly deregulated during the course of COVID-19, correlated with severity and independently associated with mortality. FACT-CLINYCoD, a novel disease scoring system, adding one point for each of Follistatin>6235pg/ml, Activin-A>591pg/ml, Activin-B>249pg/ml, CRP>10.3mg/dL, LDH>427U/L, Intensive Care Unit (ICU) admission, Neutrophil/Lymphocyte-Ratio>5.6, Years of Age>61, Comorbidities>1 and D-dimers>1097ng/ml, efficiently predicted fatal outcome in an initial cohort (AUC: 0.951±0.032, p<10−6). Two independent cohorts that were used for validation indicated comparable AUC (0.958, p=0.880 and 0.924, p=0.256, respectively).ConclusionsThis study unravels strong link between Activin/Follistatin-axis and COVID-19 mortality and introduces FACT-CLINYCoD, a novel pathophysiology-based tool that allows dynamic prediction of disease outcome, supporting clinical decision making.

scholarly journals The Activin/Follistatin-axis is severely deregulated in COVID-19 and independently associated with in-hospital mortality

2021 ◽  
Author(s):  
Evgenia Synolaki ◽  
Vasileios Papadopoulos ◽  
Georgios Divolis ◽  
Olga Tsahouridou ◽  
Efstratios Gavriilidis ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Fatal Outcome ◽  
Clinical Decision ◽  
Activin A ◽  
Serum Samples ◽  
Dynamic Prediction ◽  
Neutrophil Lymphocyte Ratio ◽  
Over Expression ◽  
Initial Cohort ◽  
Natural Inhibitor

Abstract Background Activins are members of the TGFβ-superfamily implicated in the pathogenesis of several immuno-inflammatory disorders. Based on our previous studies demonstrating that over-expression of Activin-A in murine lung causes pathology sharing key features of COVID-19, we hypothesized that Activins and their natural inhibitor Follistatin might be particularly relevant to COVID-19 pathophysiology. Methods Activin-A, Activin-B and Follistatin levels were retrospectively analyzed in 574 serum samples from 263 COVID-19 patients hospitalized in three independent centers, and compared with common demographic, clinical and laboratory parameters. Optimal-scaling with ridge-regression was used to screen variables and establish a prediction model. Result The Activin/Follistatin-axis was significantly deregulated during the course of COVID-19, correlated with severity and independently associated with mortality. FACT-CLINYCoD, a novel disease scoring system, adding one point for each of Follistatin&gt;6235pg/ml, Activin-A&gt;591pg/ml, Activin-B&gt;249pg/ml, CRP&gt;10.3mg/dL, LDH&gt;427U/L, Intensive Care Unit (ICU) admission, Neutrophil/Lymphocyte-Ratio&gt;5.6, Age&gt;61, Comorbidities&gt;1 and D-dimers&gt;1097ng/ml, efficiently predicted fatal outcome in an initial cohort (AUC: 0.951; 95%CI: 0.919-0.983, p&lt;10 -6). Two independent cohorts that were used for validation indicated similar AUC values. Conclusions This study unravels strong link between Activin/Follistatin-axis and COVID-19 mortality and introduces FACT-CLINYCoD, a novel pathophysiology-based tool that allows dynamic prediction of disease outcome, supporting clinical decision making.

Pediatric reference interval verification for endocrine and fertility hormone assays on the Abbott Alinity system

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mary Kathryn Bohn ◽  
Siobhan Wilson ◽  
Alexandra Hall ◽  
Khosrow Adeli
Keyword(s):  
Clinical Decision Making ◽  
De Novo ◽  
Reference Interval ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Healthy Children ◽  
Confidence Limits ◽  
Test Results ◽  
Serum Samples ◽  
Abbott Architect

Abstract Objectives The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed an extensive database of reference intervals (RIs) for several biomarkers on various analytical systems. In this study, pediatric RIs were verified for key immunoassays on the Abbott Alinity system based on the analysis of healthy children samples and comparison to comprehensive RIs previously established for Abbott ARCHITECT assays. Methods Analytical performance of Alinity immunoassays was first assessed. Subsequently, 100 serum samples from healthy children recruited with informed consent were analyzed for 16 Alinity immunoassays. The percentage of test results falling within published CALIPER ARCHITECT reference and confidence limits was determined. If ≥ 90% of test results fell within the confidence limits, they were considered verified based on CLSI guidelines. If <90% of test results fell within the confidence limits, additional samples were analyzed and new Alinity RIs were established. Results Of the 16 immunoassays assessed, 13 met the criteria for verification with test results from ≥ 90% of healthy serum samples falling within the published ARCHITECT confidence limits. New CALIPER RIs were established for free thyroxine and prolactin on the Alinity system. Estradiol required special considerations in early life. Conclusions Our data demonstrate excellent concordance between ARCHITECT and Alinity immunoassays, as well as the robustness of previously established CALIPER RIs for most immunoassays, eliminating the need for de novo RI studies for most parameters. Availability of pediatric RIs for immunoassays on the Alinity system will assist clinical laboratories using this new platform and contribute to improved clinical decision-making.

Novel biomarker signatures for idiopathic REM sleep behavior disorder

Neurology ◽  
2018 ◽  
Vol 91 (18) ◽  
pp. e1710-e1715 ◽  
Author(s):  
Stefania Mondello ◽  
Firas Kobeissy ◽  
Yehia Mechref ◽  
Jingfu Zhao ◽  
Farid R. Talih ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Clinical Decision Making ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Clinical Decision ◽  
Serum Levels ◽  
Serum Samples ◽  
Proteomics Analysis ◽  
Sleep Behavior ◽  
Altered Expression

ObjectiveTo perform a rigorous in-depth proteomics analysis to identify circulating biomarker signatures for idiopathic REM sleep behavior disorder (RBD), capable of providing new insights into the underlying pathogenic mechanisms and putative α-synuclein-related neurodegenerative processes.MethodsSerum samples from patients with idiopathic RBD (n = 9) and healthy controls (n = 10) were subjected to a thorough liquid chromatography–mass spectrometry (MS)/MS proteomics analysis using ultimate 3,000 nanoLC interfaced to an ESI-orbitrap velos. Data were analyzed with a systems biology approach to identify altered pathways in RBD.ResultsWe identified 259 proteins, 11 of which displayed significantly altered expression level in patients with RBD as compared to controls. Significant reduction in serum levels of dopamine β-hydroxylase (DBH) and vitamin D binding protein (GC) were consistent with alterations in the norepinephrinergic (NErgic) and dopaminergic systems, respectively. Additional altered protein profiles indicated that immunity, inflammation, complement, and coagulation also play a role in RBD pathophysiology.ConclusionsOur results shed light on the protein signature profile, molecular pathways, and mechanisms involved in the pathogenesis of RBD and its clinical manifestation. This knowledge opens a new avenue towards more accurate and timely diagnosis and characterization of RBD, which might ultimately translate into new therapeutic strategies with disease-modifying effects. Further evaluation of the identified markers is required to confirm their diagnostic value and potential to guide clinical decision-making.

scholarly journals Preoperative neutrophil-lymphocyte ratio predicts the risk of microvascular invasion in hepatocellular carcinoma: A meta-analysis

2019 ◽  
Vol 34 (3) ◽  
pp. 213-220 ◽  
Author(s):  
Furong Zeng ◽  
Bin Chen ◽  
Jiling Zeng ◽  
Zhiming Wang ◽  
Liang Xiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Publication Bias ◽  
Clinical Decision Making ◽  
Meta Analysis ◽  
Clinical Decision ◽  
Microvascular Invasion ◽  
Case Control Studies ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Retrospective Cohort Studies

Background: Preoperative estimation of microvascular invasion is of great significance for the clinical decision making in hepatocellular carcinoma. Neutrophil-lymphocyte ratio (NLR) has been reported to be correlated with the poor prognosis of hepatocellular carcinoma. However, the conclusions are conflicting on whether high preoperative NLR level is associated with the presence of microvascular invasion. Aim: To evaluate the association between preoperative NLR level and the risk of microvascular invasion in hepatocellular carcinoma. Methods: Relevant studies were identified by searching PubMed and Embase through February 2019. Fixed or random models were applied to analyze the data based on the heterogeneity. Subgroup, sensitivity, and publication bias analyses were performed. Review Manager 5.3 and STATA software were used for the meta-analysis. Results: A total of 15 studies were eventually included in this meta-analysis. Pooled data based on retrospective cohort studies showed there are more hepatocellular carcinoma patients with vascular invasion (OR 1.74; 95% Cl 1.42, 2.12; P < 0.001) and microvascular invasion (OR 1.62 95% Cl 1.39, 1.89; P < 0.001) in the high NLR group than in the low NLR group. Of case-control studies, a higher preoperative NLR level was found in the microvascular invasion positive group than in the microvascular invasion negative group (OR 0.62; 95% Cl 0.35, 0.90; P < 0.001). The subgroup, sensitivity, and publication bias analyses did not change the results. Conclusion: A higher preoperative NLR level is positively correlated with the risk of microvascular invasion in hepatocellular carcinoma.

A new strategy implementing mass spectrometry in the diagnosis of congenital disorders of N-glycosylation (CDG)

2021 ◽  
Vol 59 (1) ◽  
pp. 165-171
Author(s):  
Bruno Casetta ◽  
Sabrina Malvagia ◽  
Silvia Funghini ◽  
Diego Martinelli ◽  
Carlo Dionisi-Vici ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Congenital Disorders ◽  
Type I ◽  
Post Translational Modification ◽  
Serum Samples ◽  
Mass Spectrometric Measurement ◽  
Classical Procedure ◽  
New Strategy

AbstractObjectivesCongenital disorders of N-glycosylation (CDG) are a large group of rare metabolic disorders caused by defects in the most common post-translational modification of proteins. CDGs are often difficult to diagnose as they are manifested with non-specific symptoms and signs. Analysis of serum transferrin (TRF) isoforms, as the classical procedure used to identify a CDG patient, enables to predict pathological steps in the N-linked glycosylation process.MethodsWe devised a new strategy based on liquid chromatography-mass spectrometry (LC-MS) for the analysis of TRF isoforms by combining a simple and fast sample preparation with a specific chromatographic cleanup/separation step followed by mass-spectrometric measurement. Single TRF isoform masses were obtained through reconstruction of multiply charged electrospray data collected by quadrupole-MS technology. Hereby, we report the first analyzed serum samples obtained from 20 CDG patients and 100 controls.ResultsThe ratio of desialylated isoforms to total TRF was calculated for patients and controls. CDG-Type I patients showed higher amounts of bi-sialo isoform (range: 6.7–29.6%) compared to controls (<5.5%, mean percentage 3.9%). CDG-Type II pattern showed an increased peak of tri-sialo isoforms. The mean percentage of tri-sialo-TRF was 9.3% (range: 2.9–12.9%) in controls, which was lower than that obtained from two patients with COG5-CDG and MAN1B1-CDG (18.5 and 24.5%). Intraday and between-day imprecisions were less than 9 and 16%, respectively, for bi-sialo- and less than 3 and 6% for tri-sialo-TRF.ConclusionsThis LC-MS-based approach provides a simple, sensitive and fast analytical tool for characterizing CDG disorders in a routine clinical biochemistry while improving diagnostic accuracy and speeding clinical decision-making.

What is the role of microRNA-301A expression as a diagnostic and predictive marker of biochemical recurrence for prostate cancer?

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 19-19
Author(s):  
Adnan Dervishi ◽  
Samarpit Rai ◽  
Kristy Doan Nguyen ◽  
Thomas Michael FitzGibbon ◽  
Paul Knoll ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Clinical Decision Making ◽  
Specific Antigen ◽  
Predictive Marker ◽  
Clinical Decision ◽  
Definitive Treatment ◽  
Serum Samples ◽  
Prostate Hyperplasia

19 Background: Prostate specific antigen (PSA) screening for prostate cancer (PCa) remains controversial, due to its association with an increase in overdiagnosis of clinically insignificant PCa, and overtreatment. Hence, the need for more specific biomarkers to detect PCa and determine its prognosis. MicroRNA expression has previously been demonstrated as a biomarker to detect several malignancies. Studies suggest that microRNA-301a (miR-301a) inhibits the pro-apoptotic function of RUNX3, a transcription factor, and consequently activates ROCK1-mediated survival signaling in PCa. This study establishes the role of miR-301a as a reliable biomarker that can distinguish between patients with benign prostate hyperplasia (BPH) and PCa, and predict biochemical recurrence (BCR) after definitive treatment of PCa. Methods: Serum samples and tissue from prostate biopsies were collected from patients with an elevated PSA prospectively. The expression of miR- 301a was measured via reverse transcriptase-polymerase chain reaction. Additionally, miR-301a expression was retrospectively evaluated in prostatic tissue of 50 patients with PCa, including benign tissue, and correlated with clinico-pathological characteristics to predict BCR. Immunohistochemistry was performed to confirm the molecular target of miR-301a in cancerous tissue. Results: miR-301a demonstrated a significantly higher expression (p = 0.013) in both PCa tissue (Gleason 6 & 7 PCa) and serum samples (p = 0.011) when compared to BPH. Expression of miR-301a in Gleason 6 & 7 prostatectomy specimens positively correlated with patients who developed BCR when compared to patients who did not. When compared to the current nomogram for the prediction of PCa (i.e., PSA, age, race, Gleason score, and family history), incorporation of miR-301a was associated with a superior prediction of BCR at three years post-prostatectomy. Conclusions: miR-301a expression is a valuable tool for diagnosing PCa in patients with an elevated PSA. Combining miR-301a with PSA is associated with better risk stratification of PCa patients, and may help facilitate clinical decision making.

scholarly journals Pathogenic Heparin Induced Thrombocytopenia and Thrombosis (HIT) Antibodies Determined By Simple Rapid Functional Flow Cytometry

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3801-3801
Author(s):  
Varda R Deutsch ◽  
Michal Cipok ◽  
Ilya Kirgner ◽  
Sigi Kay ◽  
Ismail Elalamy ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Clinical Decision Making ◽  
Clinical Laboratory ◽  
Control Sample ◽  
Relative Sensitivity ◽  
Clinical Decision ◽  
Positive Control ◽  
Serotonin Release ◽  
Serum Samples ◽  
Positive Events

Abstract Background: HIT diagnosis is mandatory for patient management, yet prompt determination of pathogenic antibodies remains an unmet clinical challenge. Commonly used immunoassays carry inherent limitations and functional assays which determine antibody-mediated platelet activation are not readily available being technically demanding and require high level expertise. Additionally, they are time consuming and not rapid enough to provide quick detection of the pathologic antibodies required at time of diagnosis. Aims: To overcome these limitations, we aimed to develop an easily performed functional flow cytometric assay (FCA) to rapidly detect platelet activating antibodies for the initial diagnosis and/or confirmation of HIT. Methods: Serum samples from patients clinically suspected of HIT (n=650) were tested by the PF4/H-PaGIA immunoassay (DiaMed, Switzerland). The capacity of the patient's serum to induce platelet activation in the presence of heparin was assessed by a rapid 2-hour functional FCA. Platelets were gated by CD41 expression and a positive cut-off gate of the high 2% CD62p positive events was set on normal control sample. Each assay assessed the fraction of positive events above the 2% cut-off gate of the control sample. Background fluorescence was normalized in each sample. TRAP stimulation provided the positive control. A positive test result was defined as a value ≥2 fold greater than that of the control. Results were compared to those of the radioactive serotonin-release assay (SRA) and to the clinical 4Ts score HIT presentation Results: Consecutive HIT-suspected patient samples were tested, 15.3% were positive by the PaGIA-Heparin/PF4 immunoassay and only 4.8% by FCA. When compared to TRAP, PaGIA+/FCA+ samples were 11-fold higher in fluorescence vs. PaGIA-/FCA- samples +2SD. SRA was performed on 63 samples. Of 21 SRA positive samples, 19 were positive by FCA (relative sensitivity 90.5%), and of 42 SRA negative samples, 40 were negative by FCA (specificity 95.2%). The robustness of the FCA was confirmed by an alternative calculation, using the ratio of the % platelet activation induced by patient samples/the % activated by thrombin-receptor-activating-peptide (TRAP). Platelet activation, generated by the patient samples was 11-fold higher in PaGIA+/FCA+ vs. PaGIA-/FCA- samples, confirming the high resolution of this assay to facilitate discrimination between positive and negative values. The FCA showed significantly higher correlation with the clinical presentation of HIT (4Ts score) performed on 182 patients, compared to PaGIA-Heparin/PF4 (ROC-plot analysis, AUC 0.93 vs. 0.63, p<0.001). At 92% sensitivity, the assay specificity was 96%. Conclusions: We demonstrate that pathologic HIT antibodies can be detected rapidly by routine clinical laboratory methodology. Thus, the present assay provides a feasible answer to the unmet clinical need of prompt and reliable diagnosis of true HIT. Hence, validation of this assay by other laboratories, might offer a practical replacement for the non-readily available radioactive SRA, or other complex tests, thus contributing to improved clinical decision making and patient care. Disclosures Tomer: Azapharm: Other: patent pending and consultation fees from Azapharm outside of submitted work..

scholarly journals Cerebral localization of chronic myelomonocytic leukemia: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Clémence Haméon ◽  
Cécilia Rousselot ◽  
Flavie Arbion ◽  
Justine Cibron ◽  
Jean-Philippe Cottier ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Fatal Outcome ◽  
Myeloproliferative Neoplasm ◽  
Specific Treatment ◽  
Clinical Decision ◽  
Chronic Myelomonocytic Leukemia ◽  
Case Presentation ◽  
Cerebral Localization ◽  
Brain Involvement ◽  
Myelomonocytic Leukemia

Abstract Background Chronic myelomonocytic leukemia is a myelodysplastic/myeloproliferative neoplasm characterized by the infiltration of blood and bone marrow by immature monocytes. Cerebral localization of chronic myelomonocytic leukemia has never been described. Case presentation We report the case of a Caucasian 59 year-old man with multiorgan chronic myelomonocytic leukemia infiltration, associated with uncommon brain involvement. There was no evidence of evolution to acute myeloid leukemia. The evidence of cerebral infiltration by chronic myelomonocytic leukemia was made after autopsy. Conclusions The fatal outcome of the patient raises the question of the potential benefit of early specific treatment, such as demethylating agents or intensive chemotherapy. Sharing such images of atypical and rapidly evolving chronic myelomonocytic leukemia and the disease history may help clinical decision-making in the future.

scholarly journals A novel multi-biomarker combination predicting relapse from long-term remission after discontinuation of biological drugs in rheumatoid arthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katsuya Nagatani ◽  
Eiji Sakashita ◽  
Hitoshi Endo ◽  
Seiji Minota
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Efficacy ◽  
Roc Analysis ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Infection Risk ◽  
Serum Samples ◽  
Biological Drugs ◽  
Relapse Prediction

AbstractBiological disease modifying anti-rheumatic drugs (bDMARDs) show dramatic treatment efficacy in rheumatoid arthritis (RA). Long-term use of bDMARDs, however, has disadvantages such as high costs and infection risk. Therefore, a methodology is needed to predict any future RA relapse. Herein, we report a novel multi-biomarker combination which predicts relapse after bDMARDs-withdrawal in patients in remission. Forty patients with RA in remission for more than 12 months were enrolled. bDMARDs were withdrawn and they were followed monthly for the next 24 months. Fourteen patients (35%) of 40 in the cohort remained in remission at 24 months, whereas 26 (65%) relapsed at various time-points. Serum samples obtained longitudinally from patients in remission were assessed for the relapse-prediction biomarkers and index from 73 cytokines by the exploratory multivariate ROC analysis. The relapse-prediction index calculated from the 5 cytokines, IL-34, CCL1, IL-1β, IL-2 and IL-19, strongly discriminated between patients who relapsed and those who stayed in remission. These findings could contribute to clinical decision-making as to the timing of when to discontinue bDMARDs in RA treatment.

scholarly journals Analytical comparison between two automated biochemical analyzer systems: Roche Cobas 8000 and Mindray BS2000M

2021 ◽  
Author(s):  
Mingxing Chen ◽  
Simeng Qin ◽  
Sitao Yang ◽  
Huaping Chen ◽  
Liuyi Lu ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Altman Analysis ◽  
Serum Samples ◽  
Bland Altman Analysis ◽  
Systemic Error ◽  
Biochemical Analyzer ◽  
Two Machines ◽  
Roche Cobas

Summary Background. The values of biomarkers play a central role in routine clinical decision-making. Whereas, the performances of different automated chemical analyzers remain unclear. To determine the performances of different platforms, we evaluated the capability between Roche Cobas 8000 and Mindray BS2000M.  Methods. A total of 1869 remaining serum samples were collected. CK, LDH-1, RBP, Cys-c, IgA, IgM and IgG were assessed by using paired-t test, Passing-Bablok regression analysis and Bland Altman analysis according to CLSI EP5-A3. Results. There were significant in average bias of all items between two machines (P < 0.001). Due to the 95% confidence interval of intercept A included 0, CK, LDH-1, Cys-c and IgG were not show systemic error in Passing-Bablok regression analysis. Except for IgA, the r values and correlation coefficient of all items were higher than 0.91, which showed that the correlation and consistency is good. The Bland-Altman analysis showed that two instruments had more than 95% of the points apart from CK, LDH-1, and IgA. Conclusions. It can be considered that the two instruments have good correlation and consistency in CK, LDH-1, RBP, Cys-c, IgM and IgG, and the two instruments are interchangeable and can replace each other.

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