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1.
  • Bazarian, Jeffrey J., et al. (författare)
  • Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI) : a multicentre observational study
  • 2018
  • Ingår i: Lancet Neurology. - : Lancet Publishing Group. - 1474-4422 .- 1474-4465. ; 17:9, s. 782-789
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: More than 50 million people worldwide sustain a traumatic brain injury (TBI) annually. Detection of intracranial injuries relies on head CT, which is overused and resource intensive. Blood-based brain biomarkers hold the potential to predict absence of intracranial injury and thus reduce unnecessary head CT scanning. We sought to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI.Methods: This prospective, multicentre observational trial included adults (≥18 years) presenting to participating emergency departments with suspected, non-penetrating TBI and a Glasgow Coma Scale score of 9-15. Patients were eligible if they had undergone head CT as part of standard emergency care and blood collection within 12 h of injury. UCH-L1 and GFAP were measured in serum and analysed using prespecified cutoff values of 327 pg/mL and 22 pg/mL, respectively. UCH-L1 and GFAP assay results were combined into a single test result that was compared with head CT results. The primary study outcomes were the sensitivity and the negative predictive value (NPV) of the test result for the detection of traumatic intracranial injury on head CT.Findings: Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analysable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries. 1288 (66%) patients had a positive UCH-L1 and GFAP test result and 671 (34%) had a negative test result. For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931-0·995) and an NPV of 0·996 (0·987-0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative.Interpretation: These results show the high sensitivity and NPV of the UCH-L1 and GFAP test. This supports its potential clinical role for ruling out the need for a CT scan among patients with TBI presenting at emergency departments in whom a head CT is felt to be clinically indicated. Future studies to determine the value added by this biomarker test to head CT clinical decision rules could be warranted.Funding: Banyan Biomarkers and US Army Medical Research and Materiel Command.
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2.
  • Aurora, Lindsey, et al. (författare)
  • Prognostic Utility of a Modified HEART Score When Different Troponin Cut Points Are Used.
  • 2021
  • Ingår i: Critical Pathways in Cardiology. - : Wolters Kluwer. - 1535-282X .- 1535-2811. ; 20:3, s. 134-139
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although the recommended cut point for cardiac troponin (cTn) is the 99th percentile, many institutions use cut points that are multiples higher than the 99th percentile for diagnosing acute myocardial infarction (AMI). Prior studies have shown that patients with a HEART score (HS) ≤ 3 and normal serial cTn values (modified HS) are at low risk for adverse events. This study aimed to evaluate the prognostic utility of the HS when various cTn cut points are used.METHODS: This was a substudy of High Sensitivity Cardiac Troponin T assay for RAPID Rule-out of Acute Myocardial Infarction (TRAPID-AMI), a multicenter, international trial evaluating a rapid rule-out AMI study using high-sensitivity cardiac troponin T (hs-cTnT). One-thousand two-hundred eighty-two patients were evaluated for AMI from 12 centers in Europe, United States, and Australia from 2011 to 2013. Blood samples of hs-cTnT were collected at presentation and 2 hours, and each patient had a HS calculated. The US Food and Drug Administration approved 99th percentile for hs-cTnT (19 ng/L) was used.RESULTS: There were 213 (17%) AMIs. Within 30 days, there were an additional 2 AMIs and 8 deaths. The adverse event rates at 30 days (death/AMI) for a HS ≤ 3 and nonelevated hs-cTnT over 2 hours using increasing hs-cTnT cut points ranged from 0.6% to 5.1%.CONCLUSIONS: Using the recommended 99th percentile cut point for hs-cTnT, the combination of a HS ≤ 3 with nonelevated hs-cTnT values over 2 hours identifies a low-risk cohort who can be considered for discharge from the emergency department without further testing. The prognostic utility of this strategy is greatly lessened as higher hs-cTnT cut points are used.
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3.
  • Bahrmann, Philipp, et al. (författare)
  • Quantification of Renal Function and Cardiovascular Mortality in Patients Admitted to the Emergency Department with Suspected Acute Coronary Syndromes : Results from the TRAPID-AMI Study
  • 2017
  • Ingår i: Clinical Laboratory. - 1433-6510. ; 63:9, s. 1457-1466
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Increases in the novel serum marker cystatin C are detectable much earlier in the course of chronic kidney disease (CKD) even when levels of serum creatinine are still in the normal range. A major factor causing a decrease in serum creatinine is increasing age. Patients with CKD are more likely to develop cardiovascular disease (CVD) than a healthy population and to suffer premature deaths from CVD related to CKD. The aim of this study was to investigate whether cystatin C, serum creatinine, and estimated glomerular filtration rate (eGFR) predict cardiovascular mortality in patients admitted to the emergency department (ED) with suspected acute coronary syndromes (ACS).Methods: In 1,282 patients (mean age 62 15 years, 477 women, 805 men) with suspected ACS, baseline cystatin C concentrations, serum creatinine, and estimated glomerular filtration rate (eGFR) were measured at the ED. Clinical assessment and serial high sensitivity cardiac troponin T (hs-cTnT) measurements were used for the diagnosis of ACS. Seventeen cardiovascular deaths were registered during a median follow-up of 365 days.Results: HRs from univariate Cox regression models for each of the potential biomarkers were 12.02 (95% CI 5.10 - 28.34) for cystatin C, 4.53 (1.75 - 11.70) for serum creatinine, and 0.97 (0.96 - 0.99) for eGFR. All three biomarkers showed a significant association with cardiovascular mortality in univariate analyses. The HRs from a model with all three potential biomarkers were 59.21 (95% CI 9.69 - 361.76) for cystatin C, 0.08 (0.01 - 0.58) for serum creatinine, and 0.98 (0.96 - 1.01) for eGFR. The risk association was significant for ln (cystatin C) and ln (serum creatinine).Conclusions: Results of this prospective study show that the quantification of renal function using cystatin C is useful for predicting cardiovascular mortality in patients with suspected ACS at the ED.
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4.
  • Body, Richard, et al. (författare)
  • The Use of Very Low Concentrations of High-sensitivity Troponin T to Rule Out Acute Myocardial Infarction Using a Single Blood Test
  • 2016
  • Ingår i: Academic Emergency Medicine. - : Wiley. - 1069-6563 .- 1553-2712. ; 23:9, s. 1005-1013
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recent single-center and retrospective studies suggest that acute myocardial infarction (AMI) could be immediately excluded without serial sampling in patients with initial high-sensitivity cardiac troponin T (hs-cTnT) levels below the limit of detection (LoD) of the assay and no electrocardiogram (ECG) ischemia. Objective: We aimed to determine the external validity of those findings in a multicenter study at 12 sites in nine countries. Methods: TRAPID-AMI was a prospective diagnostic cohort study including patients with suspected cardiac chest pain within 6 hours of peak symptoms. Blood drawn on arrival was centrally tested for hs-cTnT (Roche; 99th percentile = 14 ng/L, LoD = 5 ng/L). All patients underwent serial troponin sampling over 4-14 hours. The primary outcome, prevalent AMI, was adjudicated based on sensitive troponin I (Siemens Ultra) levels. Major adverse cardiac events (MACE) including AMI, death, or rehospitalization for acute coronary syndrome with coronary revascularization were determined after 30 days. Results: We included 1,282 patients, of whom 213 (16.6%) had AMI and 231 (18.0%) developed MACE. Of 560 (43.7%) patients with initial hs-cTnT levels below the LoD, four (0.7%) had AMI. In total, 471 (36.7%) patients had both initial hs-cTnT levels below the LoD and no ECG ischemia. These patients had a 0.4% (n = 2) probability of AMI, giving 99.1% (95% confidence interval [CI] = 96.7% to 99.9%) sensitivity and 99.6% (95% CI = 98.5% to 100.0%) negative predictive value. The incidence of MACE in this group was 1.3% (95% CI = 0.5% to 2.8%). Conclusions: In the absence of ECG ischemia, the detection of very low concentrations of hs-cTnT at admission seems to allow rapid, safe exclusion of AMI in one-third of patients without serial sampling. This could be used alongside careful clinical assessment to help reduce unnecessary hospital admissions.
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5.
  • Bransky, Avishay, et al. (författare)
  • A Novel Approach to Hematology Testing at the Point of Care
  • 2021
  • Ingår i: The journal of applied laboratory medicine. - : Oxford University Press (OUP). - 2576-9456 .- 2475-7241. ; 6:2, s. 532-542
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The need for rapid point-of-care (POC) diagnostics is now becoming more evident due to the increasing need for timely results and improvement in healthcare service. With the recent COVID-19 pandemic outbreak, POC has become critical in managing the spread of disease. Applicable diagnostics should be readily deployable, easy to use, portable, and accurate so that they fit mobile laboratories, pop-up treatment centers, field hospitals, secluded wards within hospitals, or remote regions, and can be operated by staff with minimal training. Complete blood count (CBC), however, has not been available at the POC in a simple-to-use device until recently. The HemoScreen, which was recently cleared by the FDA for POC use, is a miniature, easy-to-use instrument that uses disposable cartridges and may fill this gap.CONTENT: The HemoScreen's analysis method, in contrast to standard laboratory analyzers, is based on machine vision (image-based analysis) and artificial intelligence (AI). We discuss the different methods currently used and compare their results to the vision-based one. The HemoScreen is found to correlate well to laser and impedance-based methods while emphasis is given to mean cell volume (MCV), mean cell hemoglobin (MCH), and platelets (PLT) that demonstrate better correlation when the vision-based method is compared to itself due to the essential differences between the underlying technologies.SUMMARY: The HemoScreen analyzer demonstrates lab equivalent performance, tested at different clinical settings and sample characteristics, and might outperform standard techniques in the presence of certain interferences. This new approach to hematology testing has great potential to improve quality of care in a variety of settings.
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6.
  • Lee, Byung-Boong, et al. (författare)
  • Venous hemodynamic changes in lower limb venous disease : the UIP consensus according to scientific evidence
  • 2016
  • Ingår i: International Journal of Angiology. - : Springer. - 0392-9590 .- 1827-1839. ; 35:3, s. 236-352
  • Tidskriftsartikel (refereegranskat)abstract
    • There are excellent guidelines for clinicians to manage venous diseases but few reviews to assess their hemodynamic background. Hemodynamic concepts that evolved in the past have largely remained unchallenged in recent decades, perhaps due to their often complicated nature and in part due to emergence of new diagnostic techniques. Duplex ultrasound scanning and other imaging techniques which evolved in the latter part of the 20th century have dominated investigation. They have greatly improved our understanding of the anatomical patterns of venous reflux and obstruction. However, they do not provide the physiological basis for understanding the hemodynamics of flow, pressure, compliance and resistance. Hemodynamic investigations appear to provide a better correlation with post-treatment clinical outcome and quality of life than ultrasound findings. There is a far better prospect for understanding the complete picture of the patient's disability and response to management by combining ultrasound with hemodynamic studies. Accordingly, at the instigation of Dr Angelo Scuderi, the Union Internationale de Phlebologie (UIP) executive board commissioned a large number of experts to assess all aspects of management for venous disease by evidence-based principles. These included experts from various member societies including the European Venous Forum (EVF), American Venous Forum (AVF), American College of Phlebology (ACP) and Cardiovascular Disease Educational and Research Trust (CDERT). Their aim was to confirm or dispel long-held hemodynamic principles and to provide a comprehensive review of venous hemodynamic concepts underlying the pathophysiology of lower limb venous disorders, their usefulness for investigating patients and the relevant hemodynamic changes associated with various forms of treatment. Chapter 1 is devoted to basic hemodynamic concepts and normal venous physiology. Chapter 2 presents the mechanism and magnitude of hemodynamic changes in acute deep vein thrombosis indicating their pathophysiological and clinical significance. Chapter 3 describes the hemodynamic changes that occur in different classes of chronic venous disease and their relation to the anatomic extent of disease in the macrocirculation and microcirculation. The next four chapters (Chapters 4-7) describe the hemodynamic changes resulting from treatment by compression using different materials, intermittent compression devices, pharmacological agents and finally surgical or endovenous ablation. Chapter 8 discusses the unique hemodynamic features associated with alternative treatment techniques used by the CHIVA and ASVAL. Chapter 9 describes the hemodynamic effects following treatment to relieve pelvic reflux and obstruction. Finally, Chapter 10 demonstrates that contrary to general belief there is a moderate to good correlation between certain hemodynamic measurements and clinical severity of chronic venous disease. The authors believe that this document will be a timely asset to both clinicians and researchers alike. It is directed towards surgeons and physicians who are anxious to incorporate the conclusions of research into their daily practice. It is also directed to postgraduate trainees, vascular technologists and bioengineers, particularly to help them understand the hemodynamic background to pathophysiology, investigations and treatment of patients with venous disorders. Hopefully it will be a platform for those who would like to embark on new research in the field of venous disease.
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7.
  • McCord, James, et al. (författare)
  • Prognostic Utility of a Modified HEART Score in Chest Pain Patients in the Emergency Department
  • 2017
  • Ingår i: Circulation. Cardiovascular Quality and Outcomes. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-7713 .- 1941-7705. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-The TRAPID-AMI trial study ( High-Sensitivity Troponin-T Assay for Rapid Rule-Out of Acute Myocardial Infarction) evaluated high-sensitivity cardiac troponin-T ( hs-cTnT) in a 1-hour acute myocardial infarction ( AMI) exclusion algorithm. Our study objective was to evaluate the prognostic utility of a modified HEART score ( m-HS) within this trial. Methods and Results-Twelve centers evaluated 1282 patients in the emergency department for possible AMI from 2011 to 2013. Measurements of hs-cTnT ( 99th percentile, 14 ng/L) were performed at 0, 1, 2, and 4 to 14 hours. Evaluation for major adverse cardiac events ( MACEs) occurred at 30 days ( death or AMI). Low-risk patients had an m-HS <= 3 and had either hs-cTnT<14 ng/L over serial testing or had AMI excluded by the 1-hour protocol. By the 1-hour protocol, 777 ( 60%) patients had an AMI excluded. Of those 777 patients, 515 ( 66.3%) patients had an m-HS <= 3, with 1 ( 0.2%) patient having a MACE, and 262 ( 33.7%) patients had an m-HS <= 4, with 6 ( 2.3%) patients having MACEs ( P=0.007). Over 4 to 14 hours, 661 patients had a hs-cTnT<14 ng/L. Of those 661 patients, 413 ( 62.5%) patients had an m-HS <= 3, with 1 ( 0.2%) patient having a MACE, and 248 ( 37.5%) patients had an m-HS >= 4, with 5 ( 2.0%) patients having MACEs ( P=0.03). Conclusions-Serial testing of hs-cTnT over 1 hour along with application of an m-HS identified a low-risk population that might be able to be directly discharged from the emergency department.
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8.
  • McCord, James, et al. (författare)
  • Symptoms Predictive of Acute Myocardial Infarction in the Troponin Era : Analysis From the TRAPID-AMI Study.
  • 2019
  • Ingår i: Critical Pathways in Cardiology. - 1535-282X .- 1535-2811. ; 18:1, s. 10-15
  • Tidskriftsartikel (refereegranskat)abstract
    • The TRAPID-AMI (High Sensitivity Cardiac Troponin T assay for rapid Rule-out of Acute Myocardial Infarction) study evaluated a rapid "rule-out" acute myocardial infarction (AMI). We evaluated what symptoms were associated with AMI as part of a substudy of TRAPID-AMI. There were 1282 patients evaluated from 12 centers in Europe, the United States of America, and Australia from 2011 to 2013. Multiple symptom variables were prospectively obtained and evaluated for association with the final diagnosis of AMI. Multivariate logistic regression analysis was done, and odds ratios (OR) were calculated. There were 213/1282 (17%) AMIs. Four independent predictors for the diagnosis of AMI were identified: radiation to right arm or shoulder [OR = 3.0; confidence interval (CI): 1.8-5.0], chest pressure (OR = 2.5; CI: 1.3-4.6), worsened by physical activity (OR = 1.7; CI: 1.2-2.5), and radiation to left arm or shoulder (OR = 1.7; CI: 1.1-2.4). In the entire group, 131 (10%) had radiation to right arm or shoulder, 897 (70%) had chest pressure, 385 (30%) worsened with physical activity, and 448 (35%) had radiation to left arm or shoulder. Duration of symptoms was not predictive of AMI. There were no symptoms predictive of non-AMI. Relationship between AMI size and symptoms was also studied. For 213 AMI patients, cardiac troponins I values were divided into 4 quartiles. Symptoms including pulling chest pain, supramammillary right location, and right arm/shoulder radiation were significantly more likely to occur in patients with larger AMIs. In a large multicenter trial, only 4 symptoms were associated with the diagnosis of AMI, and no symptoms that were associated with a non-AMI diagnosis.
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9.
  • Mueller, Christian, et al. (författare)
  • Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T
  • 2016
  • Ingår i: Annals of Emergency Medicine. - : Elsevier BV. - 0196-0644 .- 1097-6760. ; 68:1, s. 76-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Study objective: We aim to prospectively validate the diagnostic accuracy of the recently developed 0-h/1-h algorithm, using high-sensitivity cardiac troponin T (hs-cTnT) for the early rule-out and rule-in of acute myocardial infarction. Methods: We enrolled patients presenting with suspected acute myocardial infarction and recent (<6 hours) onset of symptoms to the emergency department in a global multicenter diagnostic study. Hs-cTnT (Roche Diagnostics) and sensitive cardiac troponin I (Siemens Healthcare) were measured at presentation and after 1 hour, 2 hours, and 4 to 14 hours in a central laboratory. Patient triage according to the predefined hs-cTnT 0-hour/1-hour algorithm (hs-cTnT beloow 12 ng/L and Delta 1 hour below 3 ng/L to rule out; hs-cTnT at least 52 ng/L r Delta 1 hour at least 5 ng/L to rule in; remaining patients to the "observational zone") was compared against a centrally adjudicated final diagnosis by 2 independent cardiologists (reference standard). The final diagnosis was based on all available information, including coronary angiography and echocardiography results, follow-up data, and serial measurements of sensitive cardiac troponin I, whereas adjudicators remained blinded to hs-cTnT. Results: Among 1,282 patients enrolled, acute myocardial infarction was the final diagnosis for 213 (16.6%) patients. Applying the hs-cTnT 0-hour/1-hour algorithm, 813 (63.4%) patients were classified as rule out, 184 (14.4%) were classified as rule in, and 285 (22.2%) were triaged to the observational zone. This resulted in a negative predictive value and sensitivity for acute myocardial infarction of 99.1% (95% confidence interval [CI] 98.2% to 99.7%) and 96.7% (95% CI 93.4% to 98.7%) in the rule-out zone (7 patients with false-negative results), a positive predictive value and specificity for acute myocardial infarction of 77.2% (95% CI 70.4% to 83.0%) and 96.1% (95% CI 94.7% to 97.2%) in the rule-in zone, and a prevalence of acute myocardial infarction of 22.5% in the observational zone. Conclusion: The hs-cTnT 0-hour/1-hour algorithm performs well for early rule-out and rule-in of acute myocardial infarction.
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10.
  • Mueller-Hennessen, Matthias, et al. (författare)
  • Combined testing of copeptin and high-sensitivity cardiac troponin T at presentation in comparison to other algorithms for rapid rule-out of acute myocardial infarction
  • 2019
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 276, s. 261-267
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We aimed to directly compare the diagnostic and prognostic performance of a dual maker strategy (DMS) with combined testing of copeptin and high-sensitivity (hs) cardiac troponin T (cTnT) at time of presentation with other algorithms for rapid rule-out of acute myocardial infarction (AMI).METHODS: 922 patients presenting to the emergency department with suspected AMI and available baseline copeptin measurements qualified for the present TRAPID-AMI substudy. Diagnostic measures using the DMS (copeptin <10, <14 or < 20 pmol/L and hs-cTnT≤14 ng/L), the 1 h-algorithm (hs-cTnT<12 ng/L and change <3 ng/L at 1 h), as well as the hs-cTnT limit-of-blank (LoB, <3 ng/L) and -detection (LoD, <5 ng/L) were compared. Outcomes were assessed as combined end-points of death and myocardial re-infarction.RESULTS: True-negative rule-out using the DMS could be achieved in 50.9%-62.3% of all patients compared to 35.0%, 45.3% and 64.5% using LoB, LoD or the 1 h-algorithm, respectively. The DMS showed NPVs of 98.1%-98.3% compared to 99.2% for the 1 h-algorithm, 99.4% for the LoB and 99.3% for the LoD. Sensitivities were 93.5%-94.8%, as well as 96.8%, 98.7% and 98.1%, respectively. Addition of clinical low-risk criteria such as a HEART-score ≤ 3 to the DMS resulted in NPVs and sensitivities of 100% with a true-negative rule-out to 33.8%-41.6%. Rates of the combined end-point of death/MI within 30 days ranged between 0.2% and 0.3% for all fast-rule-out protocols.CONCLUSION: Depending on the applied copeptin cut-off and addition of clinical low-risk criteria, the DMS might be an alternative to the hs-cTn-only-based algorithms for rapid AMI rule-out with comparable diagnostic measures and outcomes.
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11.
  • Mueller-Hennessen, Matthias, et al. (författare)
  • Diagnostic and prognostic implications using age- and gender-specific cut-offs for high-sensitivity cardiac troponin T - Sub-analysis from the TRAPID-AMI study
  • 2016
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 209, s. 26-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate the impact of age-and gender-specific cut-offs for high-sensitivity cardiac troponin T (hs-cTnT) compared to the general 99th percentile hs-cTnT cut-off on diagnosis and prognosis of acute myocardial infarction (AMI).Methods: 1282 unselected patients presenting to the emergency department with suspected AMI were enrolled as part of the TRAPID-AMI study. In the present sub-analysis, reclassification of AMI diagnosis was performed by comparing the general hs-cTnT cut-off of 14 ng/L to previously proposed age-and gender-dependent hs-cTnT 99th percentile cut-offs (28 ng/L for >= 65 years, 9 ng/L for female and 15.5 ng/L for male patients). Patients were further clinically adjudicated into acute coronary syndrome (ACS) and non-ACS.Results: For patients >= 65 years, application of age-specified cut-offs resulted in a decrease of AMI from 29.8% to 18.3% in the entire cohort (n = 557) and 54.7% to 40.9% in the ACS subcohort (n = 225). Using gender-specific cut-offs, AMI-rate increased from 16.6% to 22.6% (entire cohort, n = 477) and 62.6% to 71.7% (ACS subcohort, n = 99) in women, whereas in men, rates decreased from 23.1% to 21.1% (entire cohort, n = 805) and 48.8% to 45.9% (ACS, n = 281), respectively. Age-specified cut-offs significantly reclassified patients for outcomes of 1-month and 3-month mortality in the entire and ACS cohort (14.2% net reclassification improvement, p < 0.001, respectively). Contrary, no significant differences in outcomes could be found using gender-specific cut-offs.Conclusions: While influence of gender-specific hs-cTnT cut-offs on diagnostic and prognostic reclassification was only modest in patients with suspected AMI, age-specific cut-offs showed a significant impact and may be considered for further validation.
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12.
  • Neumann, Johannes Tobias, et al. (författare)
  • Personalized diagnosis in suspected myocardial infarction
  • 2023
  • Ingår i: Clinical Research in Cardiology. - : Springer. - 1861-0684 .- 1861-0692. ; 112, s. 1288-1301
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In suspected myocardial infarction (MI), guidelines recommend using high-sensitivity cardiac troponin (hscTn)- based approaches. These require fixed assay-specific thresholds and timepoints, without directly integrating clinical information. Using machine-learning techniques including hs-cTn and clinical routine variables, we aimed to build a digital tool to directly estimate the individual probability of MI, allowing for numerous hs-cTn assays.Methods: In 2,575 patients presenting to the emergency department with suspected MI, two ensembles of machine-learning models using single or serial concentrations of six different hs-cTn assays were derived to estimate the individual MI probability ( ARTEMIS model). Discriminative performance of the models was assessed using area under the receiver operating characteristic curve (AUC) and logLoss. Model performance was validated in an external cohort with 1688 patients and tested for global generalizability in 13 international cohorts with 23,411 patients.Results: Eleven routinely available variables including age, sex, cardiovascular risk factors, electrocardiography, and hs-cTn were included in the ARTEMIS models. In the validation and generalization cohorts, excellent discriminative performance was confirmed, superior to hs-cTn only. For the serial hs-cTn measurement model, AUC ranged from 0.92 to 0.98. Good calibration was observed. Using a single hs-cTn measurement, the ARTEMIS model allowed direct rule-out of MI with very high and similar safety but up to tripled efficiency compared to the guideline- recommended strategy.Conclusion We developed and validated diagnostic models to accurately estimate the individual probability of MI, which allow for variable hs-cTn use and flexible timing of resampling. Their digital application may provide rapid, safe and efficient personalized patient care.
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13.
  • Nowak, Richard, et al. (författare)
  • High sensitivity cardiac troponin T in patients not having an acute coronary syndrome : results from the TRAPID-AMI study
  • 2017
  • Ingår i: Biomarkers. - 1354-750X .- 1366-5804. ; 22:8, s. 709-714
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To describe the baseline, 1hr and delta high sensitivity cardiac troponin (hs-cTnT) values in patients with suspected acute myocardial infarction (AMI) but without a final acute coronary syndrome (ACS) diagnosis.Materials and methods: hs-cTnT assay for RAPID rule out of acute myocardial infarction (TRAPID-AMI) was a prospective diagnostic trial that enrolled emergency department (ED) patients with suspected AMI. Final patient diagnoses were adjudicated by a clinical events committee and subjects placed in different clinical groups: AMI, unstable angina, non-ACS cardiac, non-cardiac and unknown origin. The baseline, 1hr and delta hs-cTnT values were analysed in the 902 non-ACS patients.Results: Amongst the 1282 studied the patient groups were 213 (17%) AMI, 167 (13%) unstable angina, 113 (9%) non-ACS cardiac, 288 (22%) non-cardiac and 501 (39%) unknown origin. The hs-cTnT values in the non-cardiac and unknown origin groups were combined. The median hs-cTnT values (ng/L) were higher (p<0.001) in the non-ACS cardiac compared to the non-cardiac/unknown origin group at baseline (11.8,<5) and 1hr (12.3,<5). Their negative predictive values were 0.955 (baseline) and 0.954 (1hr) for predicting non-ACS cardiac versus non-cardiac/unknown origin diagnoses.Conclusions: Hs-cTnT may help predict whether non-ACS ED patients have a final non-ACS cardiac or non-cardiac/unknown origin diagnoses.
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14.
  • Padra, Médea, 1986, et al. (författare)
  • Mucin Binding to Moraxella catarrhalis During Airway Inflammation is Dependent on Sialic Acid.
  • 2021
  • Ingår i: American journal of respiratory cell and molecular biology. - 1535-4989. ; 65:6, s. 593-602
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic obstructive pulmonary disease (COPD) is associated with colonization by bacterial pathogens and repeated airway infections, leading to exacerbations and impaired lung function. The highly glycosylated mucins in the mucus lining the airways are an important part of the host defense against pathogens. However, mucus accumulation can contribute to COPD pathology. Here, we examined whether inflammation is associated with glycosylation changes that affect interactions between airway mucins and pathogens. We isolated mucins from lower airway samples (LAS, n=4-9) from long-term smokers with and without COPD and from never-smokers. The most abundant terminal glycan moiety was N-acetylneuraminic acid (Neu5Ac) among smokers with and without COPD and N-acetyl-hexoseamine among never-smokers. Moraxella catarrhalis bound to MUC5 mucins from smokers with and without COPD. M. catarrhalis binding correlated with inflammatory parameters and Neu5Ac content. M. catarrhalis binding was abolished by enzymatic removal of Neu5Ac. Furthermore, M. catarrhalis bound to α2-6 sialyl-lactose suggesting that α2-6 sialic acid contributes to M. catarrhalis binding to mucins. Further, we detected more M. catarrhalis binding to mucins from patients with pneumonia than to those from control subjects (n=8-13) and this binding correlated with C-reactive protein and Neu5Ac levels. These results suggest a key role of inflammation induced Neu5Ac in adhesion of M. catarrhalis to airway mucins. Inflammation induced ability of MUC5 mucins to bind M. catarrhalis is likely a host defense mechanism in the healthy lung, although it cannot be excluded that impaired mucociliary clearance limits the effectiveness of this defense in COPD patients.
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