scholarly journals Everolimus-Induced Immune Effects after Heart Transplantation: A Possible Tool for Clinicians to Monitor Patients at Risk for Transplant Rejection

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1373
Author(s):  
Kristin Klaeske ◽  
Sven Lehmann ◽  
Robert Palitzsch ◽  
Petra Büttner ◽  
Markus J. Barten ◽  
...  
Keyword(s):  
At Risk ◽  
Flow Cytometry ◽  
Heart Transplantation ◽  
Transplant Rejection ◽  
Principal Component ◽  
Immunosuppressive Regimen ◽  
Patient Specific ◽  
Monitoring Tool ◽  
Immunological Monitoring ◽  
Patients At Risk

Background: Patients treated with an inhibitor of the mechanistic target of rapamycin (mTORI) in a calcineurin inhibitor (CNI)-free immunosuppressive regimen after heart transplantation (HTx) show a higher risk for transplant rejection. We developed an immunological monitoring tool that may improve the identification of mTORI-treated patients at risk for rejection. Methods: Circulating dendritic cells (DCs) and regulatory T cells (Tregs) were analysed in 19 mTORI- and 20 CNI-treated HTx patients by flow cytometry. Principal component and cluster analysis were used to identify patients at risk for transplant rejection. Results: The percentages of total Tregs (p = 0.02) and CD39+ Tregs (p = 0.05) were higher in mTORI-treated patients than in CNI-treated patients. The principal component analysis revealed that BDCA1+, BDCA2+ and BDCA4+ DCs as well as total Tregs could distinguish between non-rejecting and rejecting mTORI-treated patients. Most mTORI-treated rejectors showed higher levels of BDCA2+ and BDCA4+ plasmacytoid DCs and lower levels of BDCA1+ myeloid DCs and Tregs than mTORI non-rejectors. Conclusion: An mTORI-based immunosuppressive regimen induced a sufficient, tolerance-promoting reaction in Tregs, but an insufficient, adverse effect in DCs. On the basis of patient-specific immunological profiles, we established a flow cytometry-based monitoring tool that may be helpful in identifying patients at risk for rejection.

QUANTIFICATION OF PREFORMED HLA ANTIBODIES BY FLOW CYTOMETRY IDENTIFIES PATIENTS AT RISK FOR STEROID RESISTANT AND STEROID SENSITIVE LIVER TRANSPLANT REJECTION.

2000 ◽  
Vol 69 (Supplement) ◽  
pp. S183-S184
Author(s):  
Juan C. Scornik ◽  
Willem J. Van der Werf ◽  
Alan W. Hemming ◽  
Alan I. Reed ◽  
Consuelo Soldevilla Pico ◽  
...  
Keyword(s):  
At Risk ◽  
Flow Cytometry ◽  
Liver Transplant ◽  
Transplant Rejection ◽  
Hla Antibodies ◽  
Steroid Resistant ◽  
Patients At Risk ◽  
Steroid Sensitive ◽  
Liver Transplant Rejection

Abstract 344: Circulating MicroRNA Signature as a Predictive Biomarker for Postoperative Heart Failure

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Farhan Rizvi ◽  
Stacie Kroboth ◽  
Larisa Emelyanova ◽  
Gracious R Ross ◽  
Maharaj Singh ◽  
...  
Keyword(s):  
Heart Failure ◽  
At Risk ◽  
Previous History ◽  
Surgical Techniques ◽  
Principal Component ◽  
Mortality Prediction ◽  
Circulating Microrna ◽  
Cardiac Events ◽  
Diagnostic Potential ◽  
Patients At Risk

Background: Advancements in cardiac surgical techniques have led to decreasing operative risk. However, postoperative heart failure (PoHF) continues to be a major risk factor for adverse cardiac events in 20-35% of patients after cardiac surgery, with a 10-fold increase in 30-day mortality. Prediction of PoHF is challenging, particularly in patients with preserved ventricular function. Circulating microRNAs (miRNAs) recently were identified to predict HF or AF after surgery, but their role in predicting PoHF is not known. This study aimed to find novel noninvasive circulating biomarkers along with clinical factors that can identify patients at risk of developing PoHF immediately after surgery. Methods: Patients undergoing CABG surgery with no previous history of HF, ventricular or supraventricular tachycardia were recruited, and preoperative blood assessed for circulating levels of protein biomarkers using ELISA. Differences in relative plasma levels of 13 miRNAs between the PoHF and no-PoHF groups were assessed by qPCR. Preoperative echocardiography was obtained. SAS was used for statistical analysis and ROC curve. Results: Out of 68 patients, 13 developed PoHF (19.1%, mean age 64.1±11.6y, 53.8% males), whereas 55 (mean age 68.3±12.4y) remained free of HF. Patients who developed PoHF had lower LVEF (51.4±13.7 vs 58.2±9.9, P<0.05) with no differences in prevalence of hypertension, diabetes, hyperlipidemia, obesity, previous myocardial infarction, stroke, COPD, sleep apnea, or use of cardiac medications. The correlation matrix of all 13 miRNAs was transformed in a principal component (PC), resulting in 3 main clusters with eigenvalue >1. PC cluster2 consisted of miR-23a, -23b, -25 and -26a2, principally involved in oxidatives stress, fibrosis and contractility, and had the strongest association (AUC=0.797; P<0.01) with PoHF. A model combining PC cluster2 with age and LVEF improved sensitivity and specificity of the model to identify patients at risk of PoHF (AUC=0.880; 95% CL, 0.761-0.991; P<0.001) Conclusion: Our study demonstrates that miR-23a, -23b, -25 and -26a2 may be useful predictors of PoHF. Circulating miRNA as biomarkers may have diagnostic potential to preoperatively, noninvasively identify patients at risk of developing PoHF.

scholarly journals Fast Tac Metabolizers at Risk – It is Time for a C/D Ratio Calculation

2019 ◽  
Vol 8 (5) ◽  
pp. 587 ◽  
Author(s):  
Schütte-Nütgen ◽  
Thölking ◽  
Steinke ◽  
Pavenstädt ◽  
Schmidt ◽  
...  
Keyword(s):  
At Risk ◽  
Graft Survival ◽  
Graft Function ◽  
Rejection Rate ◽  
Immunosuppressive Regimen ◽  
Metabolism Rate ◽  
Daily Dose ◽  
Patients At Risk ◽  
Slow Metabolizers ◽  
Patient And Graft Survival

Tacrolimus (Tac) is a part of the standard immunosuppressive regimen after renal transplantation (RTx). However, its metabolism rate is highly variable. A fast Tac metabolism rate, defined by the Tac blood trough concentration (C) divided by the daily dose (D), is associated with inferior renal function after RTx. Therefore, we hypothesize that the Tac metabolism rate impacts patient and graft survival after RTx. We analyzed all patients who received a RTx between January 2007 and December 2012 and were initially treated with an immunosuppressive regimen containing Tac (Prograf®), mycophenolate mofetil, prednisolone and induction therapy. Patients with a Tac C/D ratio <1.05 ng/mL × 1/mg at three months after RTx were characterized as fast metabolizers and those with a C/D ratio ≥1.05 ng/mL×1/mg as slow metabolizers. Five-year patient and overall graft survival were noticeably reduced in fast metabolizers. Further, fast metabolizers showed a faster decline of eGFR (estimated glomerular filtration rate) within five years after RTx and a higher rejection rate compared to slow metabolizers. Calculation of the Tac C/D ratio three months after RTx may assist physicians in their daily clinical routine to identify Tac-treated patients at risk for the development of inferior graft function, acute rejections, or even higher mortality.

scholarly journals The diagnostic and prognostic value of systems biology research in major traumatic and thermal injury: a review

2016 ◽  
Vol 4 ◽  
pp. 1-11 ◽  
Author(s):  
Jon Hazeldine ◽  
Peter Hampson ◽  
Janet M. Lord
Keyword(s):  
At Risk ◽  
Inflammatory Response ◽  
Thermal Injury ◽  
Adverse Outcome ◽  
Patient Specific ◽  
Metabolite Level ◽  
Good Outcome ◽  
Poor Outcome ◽  
Early Results ◽  
Patients At Risk

Abstract As secondary complications remain a significant cause of morbidity and mortality amongst hospitalised trauma patients, the need to develop novel approaches by which to identify patients at risk of adverse outcome is becoming increasingly important. Centred on the idea that patients who experience “poor” outcome post trauma elicit a response to injury that is distinct from those who experience “good” outcome, tailored therapeutics is an emerging concept aimed at improving current treatment regimens by promoting patient-specific therapies. Making use of recent advancements in the fields of genomics, proteomics and metabolomics, numerous groups have undertaken a systems-based approach to analysing the acute immune and inflammatory response to major traumatic and thermal injury in an attempt to uncover a single or combination of biomarkers that can identify patients at risk of adverse outcome. Early results are encouraging, with all three approaches capable of discriminating patients with “good” outcome from those who develop nosocomial infections, sepsis and multiple organ failure, with differences apparent in blood samples acquired as early as 2 h post injury. In particular, genomic data is proving to be highly informative, identifying patients at risk of “poor” outcome with a higher degree of sensitivity and specificity than statistical models built upon data obtained from existing anatomical and physiological scoring systems. Here, focussing predominantly upon human-based research, we provide an overview of the findings of studies that have investigated the immune and inflammatory response to major traumatic and thermal injury at the genomic, protein and metabolite level, and consider both the diagnostic and prognostic potential of these approaches.

1678: Identifying Patients at Risk for Benign Versus Life Shortening Postoperative Prostate-Specific Antigen Failure

2005 ◽  
Vol 173 (4S) ◽  
pp. 455-455
Author(s):  
Anthony V. D’Amico ◽  
Ming-Hui Chen ◽  
Kimberly A. Roehl ◽  
William J. Catalona
Keyword(s):  
At Risk ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Patients At Risk
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