High-sensitivity Assay Research Articles

Validation of a novel high-sensitivity cardiac troponin assay

Abstract Background The accuracy for early identification of non-ST-elevation myocardial infarction (NSTEMI) in the emergency department must be determined for all novel high-sensitivity cardiac troponin assays (hs-cTn). In this prospective, multi-centre study we developed rule-out algorithms for a high-sensitivity cardiac troponin I (hs-cTnI) assay and compared it to established algorithms for hs-cTnT and hs-cTnI. Methods Two rule-out algorithms for NSTEMI were developed from a derivation cohort of 977 patients assessed by the Siemens Atellica IM hs-cTnI assay. Diagnostic performance was compared with hs-cTnT (Roche) and hs-cTnI (Abbott) algorithms. The derived algorithms were tested in two different validation cohorts (n=518 and n=405, respectively). Results An admission sample algorithm (hs-cTnI (Siemens)) for rule-out of NSTEMI with cutoff <5 ng/L had negative predictive value (NPV) 99.4–100.0%, sensitivity 98.3–100% and specificity 46.7–56.5% in the two validation cohorts. Sensitivity and NPV was similar, specificity trended towards improvement over the comparator algorithms (Figure 1). A 0–1 hour algorithm (hs-cTnI (Siemens)) with cutoff <10 ng/L and Δ change <3 ng/L achieved sensitivity and NPV 100% with specificity >70% in both validation cohorts, similar to the comparator algorithms (Table 1). Conclusions Rule-out algorithms from the Siemens Atellica hs-cTnI assay has comparable diagnostic accuracy to established hs-cTn rule-out algorithms. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Public grant: Western Norway Regional Health Authority.Private company funding: Siemens Healthineers AG

Cardiac troponin T degradation in end-stage renal disease patients appears to occur in vivo

Abstract Background Cardiac troponin T (cTnT) is a cornerstone biomarker for diagnosing myocardial infarction (MI). However, since the introduction of the high-sensitivity assays, cardiac troponins are also measured in pathologies with cardiac risk factors, such as end-stage renal disease (ESRD), making it more difficult for clinicians to diagnose MI. Previous studies of our group identified specific larger cTnT proteoforms for the acute phase of MI, while a study in serum of ESRD patients showed solely small cTnT fragments. However, others allocated the small cTnT fragments in serum of ESRD patients to a pre-analytic effect due to abundant thrombin generation in serum, as thrombin is known to cause fragmentation of cTnT. Purpose This study investigated the effect of multiple anticoagulation methods on cTnT proteoforms in vitro and in the blood of ESRD patients. Methods First, cTnT negative serum and lithium-heparinized (LH), ethylenediaminetetraacetic-acid (EDTA), and hirudin plasma tubes were spiked with human cTnT standard, incubated at 37°C till 48 hours, and analysed with Western Blotting using anti-cTnT Roche antibodies. Second, similar blood tubes were collected from ESRD patients (n=10) conform the Declaration of Helsinki, patient samples and spiked cTnT standards were separated using gel filtration chromatography (GFC) and cTnT was subsequently analysed using the Cobas 6000 analyser. Results After 48 hours of in vitro incubation of cTnT in hirudin plasma, no cTnT degradation was observed, while LH only showed minor degradation of 10% from intact 40 kDa cTnT to 29 kDa fragments (figure 1). Also, for both EDTA and serum, a time-dependent degradation from 40 kDa cTnT to 29 kDa fragments to 15–18 kDa fragments was observed. Moreover, in ESRD patients, GFC elution profiles of all blood tubes revealed that 85–98% of cTnT corresponded to small 15–18 kDa fragments (41–42 mL), while 2–15% were 29/40 kDa cTnT forms (27–28 mL). For comparison, standards of ternary T-I-C complex and intact cTnT eluted at 21 mL and 28 mL, respectively. Conclusions The extent of cTnT degradation in vitro is dependent on the anticoagulation method of the blood tubes, with absence of degradation exclusively in hirudin plasma. Since in ESRD patients for all blood tubes mainly small 15–18 kDa cTnT fragments were found, including hirudin plasma, cTnT degradation appears to occur in vivo. This observation supports the hypothesis that larger cTnT proteoforms might indeed be specific for the acute phase of MI, thereby supporting the opportunity for developing a more specific cTnT method. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ZonMw Veni grant

Ultrasensitive aptamer-functionalized Cu-MOF fluorescent nanozyme as an optical biosensor for detection of C-reactive protein

In the present work, an aptasensing method based on integration of RNA on Cu-MOF was developed for detection of C-Reactive Protein (CRP). Cu-MOF showed stimulated fluorescence and mimetic peroxidase enzymatic activity at the time and can be used as dual-signal transduction. CRP binding RNA was used as a highly selective recognition element and immobilized on the Cu-MOF. The immobilized RNA can block the peroxidase activity and fluorescence of the signal traducer probe. Adding CRP to the RNA/Cu-MOF will release RNA from the surface of Cu-MOF and recover both the stimulated fluorescence and peroxidase activity. A biosensor was built for detection of CRP using the two modes of transduction, either colorimetry or fluorometry. A dynamic linear range was obtained from 0.1 to 50 ng mL −1with a limit of detection (LOD) as small as 40 pg mL −1was calculated in fluorescence mode and 240 pg mL −1 as LOD in colorimetry mode. The LODs are lower than the LOD of nephelometric techniques used in clinical practice and is comparable to the normal clinical cutoff value in high-sensitivity CRP assays (1 μg/mL). The aptasensor was successfully applied for detection of CRP in Covid-19 patients with spike recoveries between 84 and 102% and RSD from 0.94% to 2.05%.

Synopsis of Biomarkers of Atheromatous Plaque Formation, Rupture and Thrombosis in the Diagnosis of Acute Coronary Syndromes.

Acute coronary syndrome is the main cause of mortality and morbidity worldwide and early diagnosis is a challenge for clinicians. Though cardiac Troponin, the most commonly used biomarker, is the gold standard for myocardial necrosis, it is blind for ischemia without necrosis. Therefore, ideal biomarkers are essential in the care of patients presenting with symptoms suggestive of cardiac ischemia. The ideal biomarker or group of biomarkers of atheromatous plaque formation, rupture and thrombosis for timely and accurate diagnosis of acute coronary syndrome is a current need. Therefore, we discuss the existing understanding and future of biomarkers of atheromatous plaque formation, rupture and thrombosis of acute coronary syndrome in this review. Keywords were searched from Medline, ISI, IBSS and Google Scholar databases. Further, the authors conducted a manual search of other relevant journals and reference lists of primary articles. The development of high-sensitivity troponin assays facilitates earlier exclusion of acute coronary syndrome, contributing to a reduced length of stay at the emergency department, and earlier treatment resulting in better outcomes. Although researchers have investigated biomarkers of atheromatous plaque formation, rupture and thrombosis to help early diagnosis of cardiac ischemia, most of them necessitate validation from further analysis. Among these biomarkers, pregnancy-associated plasma protein-A, intercellular adhesion molecule-1, and endothelial cell-specific molecule- 1(endocan) have shown promising results in the early diagnosis of acute coronary syndrome but need further evaluation. However, the use of a combination of biomarkers representing varying pathophysiological mechanisms of cardiac ischemia will support risk assessment, diagnosis and prognosis in these patients and this is the way forward.

Performance analysis of Luminex and ELISA to profile serum IP-10 as a biomarker in systemic lupus erythematosus.

Interferon-γ inducible protein-10 (IP-10) is a promising biomarker in systemic lupus erythematosus (SLE). The optimal quantification platform has not yet been identified. We compared the performance of bead-based multiplex assay (Luminex) and high-sensitivity enzyme-linked immunosorbent assay (hs-ELISA) for profiling serum IP-10 as a biomarker of lupus activity. A cross-sectional study was conducted on outpatients with SLE. Serum IP-10 was measured simultaneously on Luminex and hs-ELISA, and correlation between platforms was assessed. Additionally, IP-10 levels were tested against disease activity and organ involvement. One-hundred and forty-one patients (88% women; 38 years old) were studied. Median IP-10 levels were 100.9 (125.2) pg/mL by Luminex and 156.5 (191.7) pg/mL by hs-ELISA. Correlation analysis showed Spearman's ρ = 0.621 (p < 0.0001) between Luminex and hs-ELISA. Quantification of IP-10 by Luminex showed a significant correlation (ρ = 0.198; p = 0.021) with disease activity, while this was not observed (ρ = 0.036; p = 0.683) when measured using hs-ELISA. Serum IP-10 levels were lower in quiescent patients than in those with active disease (70.8 [68.4] versus 114.3 [123.9] pg/mL; p = 0.024), with an AUC-ROC = 0.62 (p = 0.029), sensitivity = 47.9%, specificity = 77.5%, and positive likelihood ratio = 2.1. Patients with active arthritis had higher IP-10 levels than non-arthritis patients (158.1 [505.4] versus 94.1 [114.0] pg/mL; p = 0.008), with an AUC-ROC = 0.73 (p = 0.0009), sensitivity = 72.7%, specificity = 66.4%, and positive likelihood ratio = 2.1. No other type of organ involvement was identified by serum IP-10. Luminex performs better than hs-ELISA as a quantification platform for IP-10 as it correlates with disease activity and identifies active arthritis in SLE.

Postoperative myocardial injury and platelet reactivity in patients undergoing vascular surgery: The platelet reactivity and postoperative myocardial injury after major vascular surgery (PROMISE) study

BackgroundPostoperative myocardial injury (PMI) after major vascular surgery, detected by elevated cardiac troponin (cTn), has been associated with morbidity and mortality. It is unclear whether the pathophysiology of PMI is determined by increased platelet activity. ObjectiveTo examine the relationship between platelet activation (P-selectin expression) and PMI in patients undergoing elective open abdominal aortic surgery. MethodsThis prospective, single-centre, observational, cohort study included 33 patients undergoing elective open abdominal aortic surgery between March 2018 and April 2021. Patients were routinely treated with aspirin. Unstimulated platelet activation was measured by platelet bound P-selectin expression (range 0–100 %). Explorative coagulation measurements were: stimulated platelet aggregation measured with the VerifyNow® assay (aspirin cartridge), with the Multiplate® analyzer (ASPI, ADP and TRAP) and stimulated coagulation status evaluated by the TEG® Hemostasis Analyzer System (global hemostasis cartridge). The primary outcome was cTn release assessed by the fifth generation high-sensitive cTn assay. Multivariable generalized linear mixed models were used to evaluate the association between platelet function and cTn concentrations over time. ResultsTen patients (30.3 %) developed PMI. Increased P-selectin expression directly after surgery was associated with the cTn concentrations over 48 h (β = 1.39 (1.1–1.75), P = 0.0064). No association was found between P-selectin measured later after surgery (at 24 h or 48 h) and cTn concentrations. Furthermore, there was no association between the explorative coagulation parameters and cTn release. ConclusionPlatelet reactivity, assessed by P-selectin expression measured directly after surgery is associated with PMI, assessed by elevated cTn concentrations in the early postoperative period in patients undergoing elective open abdominal aortic surgery.

Whats new in 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST segment elevation?

The article sumarizes the 2020 ESC Guidelines for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation. The diagnostics of ACS consists in assessment of chest pain, EKG and cardiac troponin. Troponin should be evaluated by high sensitivity assay. 0h/1h algorithms should be used to rule-in or rule-out ACS. Patients with a positive troponin have higher risk of cardivascular events and mortality and the early invasive treatment should be applied in these patients. In the guidelines several antithrombotic stretegies for different clinical conditions are mentioned, where the cornerstone for the length and intensity of antithrombotic treatment is the evaluation of bleeding risk. Further on the revascularization aspects and strategies are debated in the guidelines. Finally there are mentioned two specific conditions of ACS - Myocardioal infarction with non-obstructive coronary arteries and Spontaneous coronary artery dissection.

From the Editor’s Desk…

From the Editor’s Desk…

Saudi Heart Association Position Statement on the Use of Biomarkers for the Management of Heart Failure and Acute Coronary Syndrome.

BackgroundThe burden of acute coronary syndrome (ACS) and heart failure (HF) remains high in Saudi Arabia. Biomarkers can greatly improve the management and outcomes of these conditions, but no official guidance is available on their use in Saudi Arabia.Consensus panelAn expert panel of cardiologists, interventional cardiologists and cardiac surgeon reviewed available evidence and formulated recommendations relevant to clinical practice in Saudi Arabia.Consensus findingshigh-sensitivity cardiac troponins play a major role in the diagnosis of ACS and the exclusion of myocardial infarction in patients with HF. Natriuretic Peptides are recommended to determine the likelihood of a diagnosis of HF in a chronic setting and rapidly exclude HF in an acute setting. High-sensitivity cardiac troponins and NT-proBNP have good prognostic ability in ACS and HF. These biomarkers could also facilitate discharge planning and reduce unnecessary hospital admissions and resource wastage. The use of biomarkers should not be excessive and should abide by appropriateness criteria. High-sensitivity assays and NT-proBNP measurements are preferred.ConclusionBy outlining expert recommendations on the best practices in the use of biomarkers, the panel hopes to contribute towards a recognized updated guidance for all healthcare providers in Saudi Arabia on the evidence-based management of HF and ACS.

Kinetics of 2 different high-sensitive troponins during targeted temperature management in out-of-hospital cardiac arrest patients with acute myocardial infarction: a post hoc sub-study of a randomised clinical trial

IntroductionShort term hypothermia has been suggested to have cardio protective properties in acute myocardial infarction (AMI) by reducing infarct size as assessed by troponins. There are limited data on the kinetics of these biomarkers in comatose out-of-hospital cardiac arrest (OHCA) patients, with and without AMI, undergoing targeted temperature management (TTM) in the ICU.PurposeThe aim of this post hoc analyses was to evaluate and compare the kinetics of two high-sensitivity cardiac troponins in OHCA survivors, with and without acute myocardial infarction (AMI), during TTM of different durations [24 h (standard) vs. 48 h (prolonged)].MethodsIn a sub-cohort (n = 114) of the international, multicentre, randomized controlled study “TTH48” we measured high-sensitive troponin T (hs-cTnT), high-sensitive troponin I (hs-cTnI) and CK-MB at the following time points: Arrival, 24 h, 48 h and 72 h from reaching the target temperature range of 33 ± 1 °C. All patients diagnosed with an AMI at the immediate coronary angiogram (CAG)—18 in the 24-h group and 25 in the 48-h group—underwent PCI with stent implantation. There were no stent thromboses.ResultsBoth the hs-cTnT and hs-cTnI changes over time were highly influenced by the cause of OHCA (AMI vs. non-AMI). In contrast to non-AMI patients, both troponins remained elevated at 72 h in AMI patients. There was no difference between the two time-differentiated TTM groups in the kinetics for the two troponins.ConclusionIn comatose OHCA survivors with an aetiology of AMI levels of both hs-cTnI and hs-cTnT remained elevated for 72 h, which is in contrast to the well-described kinetic profile of troponins in normotherm AMI patients. There was no difference in kinetic profile between the two high sensitive assays. Different duration of TTM did not influence the kinetics of the troponins.Trial registration: Clinicaltrials.gov Identifier: NCT01689077, 20/09/2012.

Chest pain in the emergency department: From score to core-A prospective clinical study.

High-sensitivity troponin assay brought new challenges as we detect elevated concentration in many other diseases, and it became difficult to distinguish the real cause of this elevation. In this notion, diagnosis of acute coronary syndrome (ACS) remains a challenge in emergency department (ED).We aim to examine different approaches for rule-in and rule-out of ACS using risk scores, copeptin, and coronary computed tomography angiography (CCTA).A prospective observational study was designed to evaluate chest pain patients. Consecutive adult patients admitted to the ED with a chief complaint of chest pain due to any cause were included.All patients were followed-up for 6 months after discharge for major adverse cardiovascular events and readmissions. Admission data, ED processes, and diagnoses were analyzed.One hundred forty-six patients were included, average age was 63 ± 13.4 years, and 95 (65.1%) were male. Global Registry of Acute Coronary Events (GRACE) and History, ECG, Age, Risk factors, Troponin (HEART) scores showed good prognostic abilities, but HEART combination with copeptin improves diagnoses of myocardial infarction (area under the curve [AUC] 0.764 vs AUC 0.864 P = .0008). Patients with elevated copeptin were older, had higher risk scores, and were more likely to be admitted to hospital and diagnosed with ACS in ED. For copeptin, AUC was 0.715 (95% confidence interval 0.629–0.803), and for combination with troponin, AUC of 0.770 (0.703–0.855) did not improve rule-in of myocardial infarction. High-sensitivity troponin I assay alongside prior stroke, history of carotid stenosis, dyslipidemia, use of diuretics, and electrocardiogram changes (left bundle branch block or ST depression) are good predictors of myocardial infarction (χ² = 52.29, AUC = 0.875 [0.813–0.937], P < .001). The regression analysis showed that combination of copeptin and CCTA without significant stenosis can be used for ACS rule-out (χ² = 26.36, P < .001, AUC = 0.772 [0.681–0.863], negative predictive value of 96.25%).For rule-in of ACS, practitioner should consider not only scores for risk stratification but carefully analyze medical history and nonspecific electrocardiogram changes and even with normal troponin results, we strongly suggest thorough evaluation in chest pain unit. For rule-out of ACS combination of copeptin and CCTA holds great potential.

Anesthesia promotes acute expression of genes related to Alzheimer’s disease and latent tau aggregation in transgenic mouse models of tauopathy

BackgroundExposure to anesthesia in the elderly might increase the risk of dementia. Although the mechanism underlying the association is uncertain, anesthesia has been shown to induce acute tau hyperphosphorylation in preclinical models. We sought to investigate the impact of anesthesia on gene expression and on acute and long-term changes in tau biochemistry in transgenic models of tauopathy in order to better understand how anesthesia influences the pathophysiology of dementia.MethodsWe exposed mice with over-expressed human mutant tau (P301L and hyperdopaminergic COMTKO/P301L) to two hours of isoflurane and compared anesthetized mice to controls at several time points. We evaluated tau hyperphosphorylation with quantitative high-sensitivity enzyme-linked immunosorbent assay and performed differential expression and functional transcriptome analyses following bulk mRNA-sequencing.ResultsAnesthesia induced acute hyperphosphorylation of tau at epitopes related to Alzheimer’s disease (AD) in both P301L-based models. Anesthesia was associated with differential expression of genes in the neurodegenerative pathways (e.g., AD-risk genes ApoE and Trem2) and thermogenesis pathway, which is related to both mammalian hibernation and tau phosphorylation. One and three months after anesthesia, hyperphosphorylated tau aggregates were increased in the anesthetized mice.ConclusionsAnesthesia may influence the expression of AD-risk genes and induce biochemical changes in tau that promote aggregation even after single exposure. Further preclinical and human studies are necessary to establish the relevance of our transcriptomic and biochemical findings in these preclinical models to the pathogenesis of dementia following anesthesia.Trial registration: Not applicable.

Comparison of ADVIA Centaur ultra-sensitive and high-sensitive assays for troponin I in serum

Cardiac troponin I (cTnI) is a standard biomarker for the diagnosis of acute myocardial infarction (AMI). While older, ultra-sensitive cTnI (us-cTnI) assays use the 99th percentile as the reference threshold, newer high-sensitive cTnI (hs-cTnI) assays use the limit of detection or functional sensitivity instead. However, little has been done to systematically compare these two methods. The present study also served as a validation of hs-cTnI in our laboratory. Here, we compared the results obtained from the blood serum obtained from 8810 patients using the us-cTnI and the hs-cTnI assays run in tandem on the ADVIA Centaur XP analyser. We found that in 2279 samples the concentration of cTnI measured with the ultra-sensitive method was below the detection limit, while with the high-sensitive method, only 540 were below the detection limit. We also compared results from these assays with the ultimate diagnosis of a subset of individuals. The analysis of the results below cut-off with the ultra-sensitive method showed that this method would not detect 96 cases related to heart disorder. Overall, the main finding of our research is that hs-cTnI is the preferable option and is able to be deployed effectively in the laboratory setting.

Rationale and Design of the Cardiac CARE Trial: A Randomized Trial of Troponin-Guided Neurohormonal Blockade for the Prevention of Anthracycline Cardiotoxicity.

Anthracyclines are effective cytotoxic drugs used in the treatment of breast cancer and lymphoma but are associated with myocardial injury, left ventricular dysfunction, and heart failure. Anthracycline-induced cardiotoxicity is highly variable in severity and without a proven therapeutic intervention. β-Adrenergic receptor blockers and renin-angiotensin-system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients. The Cardiac CARE trial is a multicentre prospective randomized open-label blinded end point trial of combination β-adrenergic receptor blocker and renin-angiotensin-system inhibitor therapy in patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy that is associated with myocardial injury. Patients at higher risk of cardiotoxicity with plasma high-sensitivity cTnI (cardiac troponin I) concentrations in the upper tertile at the end of chemotherapy are randomized to standard of care plus combination candesartan and carvedilol therapy or standard of care alone. All patients undergo cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. The primary end point is the change in left ventricular ejection fraction at 6 months after chemotherapy. In low-risk nonrandomized patients, left ventricular ejection fraction before and 6 months after anthracycline will be compared with define the specificity of the high-sensitivity cTnI assay for identifying low-risk participants who do not develop left ventricular systolic dysfunction. Cardiac CARE will examine whether cardiac biomarker monitoring identifies patients at risk of left ventricular dysfunction following anthracycline chemotherapy and whether troponin-guided treatment with combination candesartan and carvedilol therapy prevents the development of left ventricular dysfunction in these high-risk patients.

Anti-Müllerian hormone levels and breast cancer risk in the study of women's health across the nation.

The relation of premenopausal anti-Müllerian hormone (AMH) levels with breast cancer risk has been evaluated in a few studies, but primarily in non-Hispanic White women. We evaluated the association of AMH levels with breast cancer risk in Study of Women's Health Across the Nation (SWAN), a multi-ethnic cohort of women. At enrollment, participants had an intact uterus and ≥ 1 ovary, and ≥ 1 menstrual period in the last 3months. AMH at first measurement was assessed in 1,529 pre- or perimenopausal women using a high-sensitivity ELISA assay; values were natural log transformed. Breast cancer diagnoses were assessed at enrollment and subsequent follow-up visits through 2018 (median 6.1years). In total, 84 women reported an incident breast cancer diagnosis. In multivariable Cox regression models adjusting for age, race and ethnicity, body mass index, and other factors, higher AMH levels were associated with a non-significant increased breast cancer risk. Compared to women in the 1st quartile, the hazard ratio (95% confidence interval) for women in the4th quartile was 1.77 (0.87-3.60). Our results did not suggest a significant association between AMH and breast cancer risk; however, estimates were consistent with prior studies that reported positive associations.

Prepregnancy body mass index, gestational weight gain, and maternal prepartum inflammation in normal pregnancies: findings from a Chinese cohort

BackgroundObesity has been linked to systemic inflammation in population studies.ObjectiveTo examine the associations of prepregnancy body mass index (pBMI) and total gestational weight gain (tGWG) with maternal prepartum low-grade inflammation (LGI) and clinically significant inflammation (CSI) defined by serum C-reactive protein (CRP) concentration.MethodsFive thousand four hundred seventy-six Chinese women with uncomplicated pregnancies and recorded data on pBMI and prepartum body weight were included in this study. Blood samples were drawn before delivery for high-sensitivity CRP assay. Inadequate, optimal, and excessive tGWG were defined using the Institute of Medicine's recommendation. Multivariable Poisson regressions were used to estimate relative risks (RRs) for having prepartum LGI and CSI (defined as CRP concentration 3–10 and > 10 mg/L, respectively) across pBMI and tGWG categories.ResultsThe mean pBMI, mean tGWG, and median maternal prepartum CRP concentration were 20.4 kg/m2, 13.9 kg, and 3.3 mg/L, respectively. The prevalence of prepartum CSI and LGI was 7.2% and 47.8%. The adjusted RRs (95% confidence interval) of CSI for normal (18.5–24.9 kg/m2) and high (≥ 25 kg/m2) vs. low pBMI (< 18.5 kg/m2) were 1.35 (1.05–1.74) and 2.28 (1.53–3.39), respectively. The respective adjusted RRs of LGI were 1.19 (1.11–1.28) and 1.59 (1.42–1.77). The adjusted RRs for excessive vs. optimal tGWG was 1.18 (0.94–1.48) for CSI and 1.14 (1.07–1.21) for LGI.ConclusionsPrepregnancy overweight/obesity and excessive tGWG increase the risk of maternal prepartum systemic inflammation, which further highlights the importance of weight management before and during pregnancy.

Association of Serum Osteoprotegerin Level With Myocardial Injury and Cardiovascular Calcification in Chronic Kidney Disease Patients.

BackgroundChronic kidney disease has emerged as a significant independent risk factor for cardiovascular disease. Cardiovascular calcification is an active process involving a complex interaction of inducers and inhibitors. High sensitivity cardiac troponin T assay detects troponin T with higher sensitivity and precision at an earlier point of time than the conventional assays, and is associated with poor outcomes. Serum osteoprotegerin is classed as an inhibitory factor for cardiovascular calcification. It is involved in the pathological processes of vascular damage and linked to the excess cardiovascular morbidity. The aim of the present study was to evaluate the extent of cardiovascular calcification and serum high sensitivity cardiac troponin T level, and their association with serum osteoprotegerin level in patients with chronic kidney disease stages 3–5.Methods90 chronic kidney disease patients were enrolled in this study, and they were divided into two groups: group (1) included 45 non-dialysis-dependent chronic kidney disease patients (stages 3–5) and group (2) included 45 chronic hemodialysis patients. Each group further subdivided according to the presence of cardiovascular calcification into subgroup A and B. Vascular calcifications were assessed by lateral lumbar, pelvis and hands X-ray radiographs. Valvular calcification was assessed by echocardiography. Serum cardiac troponin T was measured by high sensitivity assay and serum osteoprotegerin was measured by ELISA.ResultsCardiovascular calcification distribution was 22.2% in group (1) and 33.3% in group (2). Serum osteoprotegerin and troponin T in calcification groups (1A and 2A) were significantly higher than non-calcification groups (1B and 2B; P < 0.001). Osteoprotegerin correlated positively with high sensitivity cardiac troponin T (rs = 0.72, P < 0.001). cardiovascular calcification correlated positively with osteoprotegerin, troponin T, and phosphorus. osteoprotegerin and phosphorus were significant independent predictors of cardiovascular calcification at cut-off values ≥4.6 ng/L and ≥6.95 mg/dl, respectively (P < 0.001). Serum phosphorus and creatinine were independent predictors of osteoprotegerin (P < 0.001 and 0.048, respectively).ConclusionOsteoprotegerin is strongly associated with cardiovascular calcification and high sensitivity cardiac troponin T. In addition, there is a positive association between calcification and troponin T. This suggests a role for osteoprotegerin in the pathogenesis and risk stratification of cardiovascular calcification and myocardial injury in chronic kidney disease patients with a potential role as a therapeutic target.

Analytical Considerations in Deriving 99th Percentile Upper Reference Limits for High-Sensitivity Cardiac Troponin Assays: Educational Recommendations from the IFCC Committee on Clinical Application of Cardiac Bio-Markers.

The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers provides evidence-based educational documents to facilitate uniform interpretation and utilization of cardiac biomarkers in clinical laboratories and practice. The committee's goals are to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay in clinical practice. Measurement of high-sensitivity cardiac troponin (hs-cTn) assays is a cornerstone in the clinical evaluation of patients with symptoms and/or signs of acute cardiac ischemia. To define myocardial infarction, the Universal Definition of Myocardial Infarction requires patients who manifest with features suggestive of acute myocardial ischemia to have at least one cTn concentration above the sex-specific 99th percentile upper reference limit (URL) for hs-cTn assays and a dynamic pattern of cTn concentrations to fulfill the diagnostic criteria for MI. This special report provides an overview of how hs-cTn 99th percentile URLs should be established, including recommendations about prescreening and the number of individuals required in the reference cohort, how statistical analysis should be conducted, optimal preanalytical and analytical protocols, and analytical/biological interferences or confounds that can affect accurate determination of the 99th percentile URLs. This document also provides guidance and solutions to many of the issues posed.

Management of acute coronary syndrome without ST-segment elevation

The collective term acute coronary syndrome (ACS) encompasses ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS). The latter comprises unstable angina pectoris and non-ST-segment elevation myocardial infarction (NSTEMI). The diagnosis of STEMI necessitates an immediate referral to cardiac catheterization. The diagnostics and management of NSTE-ACS are more challenging. The current guidelines of the European Society of Cardiology (ESC) for treatment of NSTE-ACS were published in 2020 and deal with the topics of diagnostics, risk stratification, antithrombotic treatment, invasive or non-invasive coronary diagnostics and long-term treatment. The focus of the guidelines is on the application of high-sensitivity cardiac troponin assay(hs-cTn) combined with verified diagnostic algorithms to enable a rapid triage decision (rule-in as possible NSTEMI or rule-out as NSTEMI excluded) in the emergency room or the chest pain unit.

Chronic Pesticide Exposure in Farm Workers Is Associated with the Epigenetic Modulation of hsa-miR-199a-5p.

The increasing use of pesticides in intensive agriculture has had a negative impact on human health. It was widely demonstrated how pesticides can induce different genetic and epigenetic alterations associated with the development of different diseases, including tumors and neurological disorders. Therefore, the identification of effective indicators for the prediction of harmful pesticide exposure is mandatory. In this context, the aim of the study was to evaluate the modification of hsa-miR-199a-5p expression levels in liquid biopsy samples obtained from healthy donors and farm workers with chronic exposure to pesticides. For this purpose, the high-sensitive droplet digital PCR assay (ddPCR) was used to detect variation in the expression levels of the selected microRNA (miRNA). The ddPCR analyses revealed a significant down-regulation of hsa-miR-199a-5p observed in individuals exposed to pesticides compared to control samples highlighting the good predictive value of this miRNA as demonstrated by statistical analyses. Overall, the obtained results encourage the analysis of miRNAs as predictive biomarkers of chronic pesticide exposure thus improving the current strategies for the monitoring of harmful pesticide exposure.