High-sensitivity Assay Research Articles

The relationship between workload and exercise-induced cardiac troponin elevations is influenced by non-obstructive coronary atherosclerosis.

The relationship between exercise-induced troponin elevation and non-obstructive coronary artery disease (CAD) is unclear. This observational study assessed non-obstructive CAD's impact on exercise-induced cardiac Troponin I (cTnI) elevation in middle-aged recreational athletes. cTnI levels of 40 well-trained recreational athletes (73% males, 50 ± 9 years old) were assessed by a high-sensitive cTnI assay 24 h before, and at 3 and 24 h following two high-intensity exercises of different durations; a cardiopulmonary exercise test (CPET), and a 91-km mountain bike race. Workload was measured with power meters. Coronary computed tomography angiography was used to determine the presence or absence of non-obstructive (<50% obstruction) CAD. A total of 15 individuals had non-obstructive CAD (Atherosclerotic group), whereas 25 had no atherosclerosis (normal). There were higher post-exercise cTnI levels following the race compared with CPET, both at 3 h (77.0 (35.3-112.4) ng/L vs. 11.6 (6.4-22.5) ng/L, p < 0.001) and at 24 h (14.7 (6.7-16.3) vs. 5.0 (2.6-8.9) ng/L, p < 0.001). Absolute cTnI values did not differ among groups. Still, the association of cTnI response to power output was significantly stronger in the CAD versus Normal group both at 3 h post-exercise (Rho = 0.80, p < 0.001 vs. Rho = -0.20, p = 0.33) and 24-h post-exercise (Rho = 0.87, p < 0.001 vs. Rho = -0.13, p = 0.55). Exercise-induced cTnI elevation was strongly correlated with exercise workload in middle-aged athletes with non-obstructive CAD but not in individuals without CAD. This finding suggests that CAD influences the relationship between exercise workload and the cTnI response even without coronary artery obstruction.

Low Level of First Morning Urine Cardiac Troponin I: A Specific Hallmark of Aortic Stenosis Severity.

Background: It has recently been shown that cardiac-specific troponin I concentrations in first morning urine samples can be measured with commercially available tests. Due to their accumulation in the first morning urine, scientific papers indicate a potential predictive value for cardiovascular diseases. Therefore, the aim of this study was to compare the concentration of cardiac troponin I in the first morning urine in patients with severe aortic stenosis and the healthy population. Patients and Methods: Blood and first morning urine samples were collected from 34 healthy individuals (17 female) at University Hospital Merkur and 25 patients with severe aortic stenosis (14 female) before surgical treatment at University Hospital Dubrava. Cardiac troponin I and T values were determined using high-sensitivity assays using commercially available Abbott and Roche tests. Results: Patients with severe aortic stenosis had significantly lower troponin I concentrations in the first morning urine samples (0.3 ng/L (0.1-0.6)) as compared to the healthy population (15.2 ng/L (8.4-19.9)) (p < 0.001). There was no statistically significant difference in troponin T concentrations between healthy individuals and patients with severe aortic stenosis. In parallel, both I and T plasma troponin concentrations were significantly higher in patients with severe aortic stenosis. Conclusions: In patients with severe aortic stenosis, cardiac troponin I values in the first morning urine are significantly lower than in healthy subjects.

Exercise-induced cardiac troponin elevations and cardiac ventricular dysfunction assessed by tissue Doppler echocardiography and speckle tracking among non-elite runners in Beijing marathon

ObjectivesWe aimed to identify the major determinants of cardiac troponin changes response to exercise among non-elite runners participating in the Beijing 2022 marathon, with a particular focus on the associations with the cardiac function assessed by tissue Doppler echocardiography and speckle tracking. DesignA prospective study. MethodsA total of 33 non-elite participants in the 2022 Beijing Marathon were included in the study. Echocardiographic assessment and blood sample collection were conducted before, immediately after, and two weeks after the marathon. Blood samples were analyzed using the same Abbot high-sensitivity cTnI STAT assay. Echocardiography included tissue Doppler and speckle tracking echocardiography. ResultsFollowing the marathon, significant increases were observed in cardiac biomarkers, with hs-cTnI elevating from 3.1 [2.3–6.7] to 49.6 [32.5–76.9] ng/L (P < 0.0001). Over 72 % of participants had post-race hs-TnI levels surpassing the 99th percentile upper reference limit. There was a notable correlation between pre-marathon hs-cTnI levels (β coefficient, 0.56 [0.05, 1.07]; P = 0.042), weekly average training (β coefficient, −1.15 [−1.95, −0.35]; P = 0.009), and hs-cTnI rise post-marathon. Echocardiography revealed significant post-race cardiac function changes, including decreased E/A ratio (P < 0.0001), GWI (P < 0.0001), and GCW (P < 0.0001), with LVEF (β coefficients, 0.112 [0.01, 0.21]; P = 0.042) and RV GLS (β coefficients, 0.124 [0.01, 0.23]; P = 0.035) changes significantly associated with hs-TnI alterations. All echocardiographic and laboratory indicators reverted to baseline levels within two weeks. ConclusionsBaseline hs-cTnI levels and weekly average training influence exercise-induced hs-cTnI elevation in non-elite runners. Echocardiography revealed post-race changes in cardiac function, with LVEF and RV GLS significantly associated with hs-TnI alterations. These findings contribute to understanding the cardiac response to exercise and could guide training and recovery strategies.

External validation of a rapid algorithm using high-sensitivity troponin assay results for evaluating patients with suspected acute myocardial infarction

ObjectiveWe sought to validate the clinical performance of a rapid assessment pathway incorporating the Siemens Atellica IM high sensitivity cardiac troponin I (hs-cTnI) assay in patients presenting to the emergency...

Evaluation of Age and Sex Differences in Contemporary versus High-Sensitivity Troponin I Measurement in Hospitalized Patients.

Background: With the transition from the contemporary (cTnI) to high-sensitivity troponin assay (hs-cTnI), concerns have arisen regarding the diagnostic differences between these two assays due to analytical distinctions. This study aims to evaluate the age and sex differences between these two assays, as well as the differences resulting from using two different 99th percentile values of the high-sensitivity troponin assay. Method: A retrospective observational study was conducted at an academic medical center, encompassing a total of 449 lithium heparin plasma samples included in the dataset. Both contemporary and high-sensitivity troponin were simultaneously measured using Siemens ADVIA Centaur analyzers. Two sets of sex-specific 99th percentile URLs from the Siemens study (cutoff-1) and Universal Sample Bank data (cutoff-2) were used for the data analysis. Results: The use of cutoff-1 or cutoff-2 had a negligible impact on troponin classification. Troponin elevation significantly increased in individuals > 50 years old for males and >40 years old for females, with both troponin assays. A receiver operating characteristic analysis did not find significant differences between the two assays. The Kaplan-Meier curves showed no differences in survival in cTnI according to the non-sex-specific 99th URL or hs-cTnI (cutoff-2) but showed a slight difference in survival in hs-cTnI (cutoff-1). Conclusions: Overall, there were no significant differences in age and sex in the diagnostic performance between the contemporary and high-sensitivity troponin assays. Selection criteria for the establishment of the 99th percentile URL should be standardized to avoid the misinterpretation of the troponin results.

Abstract CT151: Trial in progress:A phase 1 trial of TSC-100 and TSC-101, engineered T cell therapies that target minor histocompatibility antigens to eliminate residual disease after hematopoietic cell transplantation

Abstract Engineered T cell therapies such as CAR-T cell therapies have transformed the treatment of B-cell but not non-B cell hematologic malignancies. Allogeneic hematopoietic cell transplantation (HCT) remains the best curative option for hematologic malignancies but ~40% of patients relapse post-HCT with up to 90% mortality due to residual disease post-HCT. A key challenge in non-B cell malignancies is identifying the right antigens for T cell targeting. Cancer-associated antigens are heterogenous, enabling rapid escape of malignant cells with low antigens, while targeting lineage-specific antigens without distinct expression in malignant versus normal myeloid cells can cause prolonged neutropenia. A potential solution is targeting minor histocompatibility antigens (MiHAs) that are homogenously expressed on all hematopoietic cells and are genetically mismatched between donors and patients undergoing HCT. These mismatches enable T cells to selectively eliminate residual patient hematopoietic cells, normal or malignant, leaving donor cells untouched. TScan has developed allogeneic donor derived T-cell products TSC-100 and TSC-101, targeting MiHAs HA-1 and HA-2 respectively, both presented on HLA-A*02:01. By choosing HCT patients who are HLA-A*02:01 positive (&amp;gt;98% of whom are either HA-1 or HA-2 positive) and donors who are either HLA-A*02:01 or MiHA negative, TSC-100 or TSC-101 can potentially eliminate all residual patient-derived hematopoietic cells after HCT, to prevent disease relapse.Study NCT05473910 is a multi-center, multi-arm, non-randomized controlled Phase 1 umbrella study evaluating the feasibility, safety and preliminary efficacy of TSC-100 and TSC-101. Inclusion criteria (Figure 1) include adults with AML, MDS or ALL eligible for reduced intensity conditioning-based haploidentical donor transplantation from HLA or MiHA mismatched donors. HLA-A*02:01-positive patients undergo HA-1/HA-2 testing and are assigned to either TSC-100 or TSC-101 treatment arms in addition to HCT. HLA-A*02:01-negative patients in the control arm receive HCT alone. Upon count recovery after HCT, patients in treatment arms receive either TSC-100 or TSC-101, administered as single or two doses. Primary endpoints include adverse event profiles and dose limiting toxicities. Secondary endpoints include relapse rates, disease-free survival and overall survival. Exploratory endpoints include surrogates of efficacy such as minimal residual disease (MRD) rates and donor chimerism rates and kinetics. MRD is measured before and after HCT using flow cytometry, NGS and ddPCR. Donor chimerism is measured by standard STR-based and novel high-sensitivity NGS-based assays to quantify residual patient-derived hematopoietic cells. Together, these assays measure elimination of residual patient hematopoietic cells, malignant or normal, and could provide early evidence of biological activity. Citation Format: Monzr Al Malki, Alla Keyzner, Hyung Suh, Uday Popat, Chen Yi-Bin, Saar Gill, Melhem Solh, Joseph Uberti, Iris Isufi, Erica Buonomo, Yun Wang, Jim Murray, Gavin MacBeath, Debora Barton, Shrikanta Chattopadhyay, Ran Reshef. Trial in progress:A phase 1 trial of TSC-100 and TSC-101, engineered T cell therapies that target minor histocompatibility antigens to eliminate residual disease after hematopoietic cell transplantation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT151.

Sex Steroid Levels in Women With Hypopituitarism: A Case-controlled Observational Study.

Women with hypopituitarism remain at increased risk of morbidity and mortality. Insufficient replacement of sex steroids has been suggested as a contributing factor, but sex steroid levels in women with hypopituitarism have not been comprehensively mapped. To quantify sex steroids in women with hypopituitarism by a high-sensitivity assay. Using a combination of clinical and biochemical criteria, women with hypopituitarism (n = 104) who started GH replacement in 1995 to 2014 at a single center were categorized as eugonadal or having hypogonadotropic hypogonadism (HH). A population-based cohort of women (n = 288) served as controls. Eugonadal women and controls were categorized as pre-/postmenopausal and HH women as younger/older (≤ or >52 years). Dehydroepiandrosterone (DHEA), androstenedione, testosterone, dihydrotestosterone, progesterone, 17αOH-progesterone, estradiol, and estrone were analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Among both premenopausal/younger and postmenopausal/older women, women with HH had lower levels of sex steroid precursors (DHEA, androstenedione) and androgens (testosterone and dihydrotestosterone) than controls. Progesterone, 17αOH-progesterone, estrone, and estradiol showed similar patterns. Women with HH and ACTH deficiency had markedly lower concentrations of all sex hormones than those without ACTH deficiency. This study demonstrates for the first time a broad and severe sex steroid deficiency in both younger and older women with HH, particularly in those with combined gonadotropin and ACTH deficiency. The health impact of low sex steroid levels in women with hypopituitarism requires further study, and women with combined gonadotropin and ACTH deficiency should be a prioritized group for intervention studies with sex hormone replacement.

Characterization of myocardial injury phenotype by thermal liquid biopsy.

With the advent and implementation of high-sensitivity cardiac troponin assays, differentiation of patients with distinct types of myocardial injuries, including acute thrombotic myocardial infarction (TMI), acute non-thrombotic myocardial injury (nTMi), and chronic coronary atherosclerotic disease (cCAD), is of pressing clinical importance. Thermal liquid biopsy (TLB) emerges as a valuable diagnostic tool, relying on identifying thermally induced conformational changes of biomolecules in blood plasma. While TLB has proven useful in detecting and monitoring several cancers and autoimmune diseases, its application in cardiovascular diseases remains unexplored. In this proof-of-concept study, we sought to determine and characterize TLB profiles in patients with TMI, nTMi, and cCAD at multiple acute-phase time points (T 0 h, T 2 h, T 4 h, T 24 h, T 48 h) as well as a follow-up time point (Tfu) when the patient was in a stable state. TLB profiles were collected for 115 patients (60 with TMI, 35 with nTMi, and 20 with cCAD) who underwent coronary angiography at the event presentation and had subsequent follow-up. Medical history, physical, electrocardiographic, histological, biochemical, and angiographic data were gathered through medical records, standardized patient interviews, and core laboratory measurements. Distinctive signatures were noted in the median TLB profiles across the three patient types. TLB profiles for TMI and nTMi patients exhibited gradual changes from T0 to Tfu, with significant differences during the acute and quiescent phases. During the quiescent phase, all three patient types demonstrated similar TLB signatures. An unsupervised clustering analysis revealed a unique TLB signature for the patients with TMI. TLB metrics generated from specific features of TLB profiles were tested for differences between patient groups. The first moment temperature (TFM) metric distinguished all three groups at time of presentation (T0). In addition, 13 other TLB-derived metrics were shown to have distinct distributions between patients with TMI and those with cCAD. Our findings demonstrated the use of TLB as a sensitive and data-rich technique to be explored in cardiovascular diseases, thus providing valuable insight into acute myocardial injury events.

Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen.

Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings.

Cardiac troponin I as predictor for cardiac and other mortality in the German randomized lung cancer screening trial (LUSI)

Cardiac Troponin I (cTnI) could be used to identify individuals at elevated risk of cardiac death in lung cancer (LC) screening settings. In a population-based, randomized LC screening trial in Germany (“LUSI” study) serum cTnI was measured by high-sensitivity assay in blood samples collected at baseline, and categorized into unquantifiable/low (< 6 ng/L), intermediate (≥ 6–15 ng/L), and elevated (≥ 16 ng/L). Cox proportional-hazard models were used to estimate risk of all-cause and cardiac mortality with cTnI levels. After exclusion criteria, 3653 participants were included for our analyses, of which 82.4% had low, 12.8% intermediate and 4.8% elevated cTnI, respectively. Over a median follow up of 11.87 years a total of 439 deaths occurred, including 67 caused by cardiac events. Within the first 5 years after cTnI measurement, intermediate or elevated cTnI levels showed approximately 1.7 (HR = 1.69 [95% CI 0.57–5.02) and 4.7-fold (HR = 4.66 [1.73–12.50]) increases in risk of cardiac death relative to individuals with unquantifiable/low cTnI, independently of age, sex, smoking and other risk factors. Within this time interval, a risk model based on age, sex, BMI, smoking history and cTnI showed a combined area under the ROC curve (AUC) of 73.6 (58.1–87.3), as compared to 70.4 (53.3–83.5) for a model without cTnI. Over the time interval of > 5–10 years after blood donation, the relative risk associations with cTnI and were weaker. cTnI showed no association with mortality from any other (non-cardiac) cause. Our findings show that cTnI may be of use for identifying individuals at elevated risk specifically of short-term cardiac mortality in the context of LC screening.

Roots applicable, high sensitivity and specificity assay for the detection of Candidatus Liberibacter asiaticus in citrus roots and fruits.

Candidatus Liberibacter asiaticus (CLas), a phloem-limited Gram-negative bacterium, is associated with citrus huanglongbing (HLB), which is one of the most destructive diseases currently threatening citrus production worldwide. No effective treatment for HLB is currently available. Effective prevention and control in the initial stage can block the spread and disease progression of HLB. Herein, we developed a co-detection assay for the 16S rDNA and 16S rRNA of CLas, the sensitivity of the co-detection assay was significantly increased over that of the single CLas DNA detection system. Beyond this, we found that the co-detection assay was a better fit to the root samples with higher population abundance than the previous reported detection system because it has a better specificity. Moreover, we found that the contents of 16S rRNA of CLas in citrus roots and fruits are significantly higher than that in leaves, which suggests that the time of HLB diagnosis is probably earlier by using these special tissues and the replication of CLas may become more active in these tissues, further suggested that the significance of study the mechanism of infection, prevention and control of HLB staring from these tissues.

Abstract 5016: Building better contrived samples to properly evaluate Next-generation MRD and LBx assays

Abstract Circulating tumor DNA (ctDNA) is a component of cell-free DNA (cfDNA) that originates from tumor tissue in the plasma of cancer patients. Although ctDNA is a broadly applicable tumor biomarker, the absolute amount of ctDNA varies across indication and stage, with the level of ctDNA present reflective of tumor volume. As novel methods for the characterization of ctDNA develop, there is need to evaluate these assays with appropriate samples. But current commercial reference standards, generated from modified cell lines or oligonucleotides lack important features such as DNA methylation, fragmentation pattern and nucleosome positioning, whilst clinical trial samples lack the required volume to perform multiple tests and often lack proper consent. We have created a framework for generating contrived samples containing the biological features of clinical samples and the attributes of a reference standard. The plasma-in-plasma contrived samples are generated from commercially purchased and fully consented matched tumor and plasma from cancer patients with age and gender matched healthy donor plasma. Samples are characterized by an internally validated 700 gene NGS panel to identify somatic variants and copy number alterations, which establishes ‘ground truth’. A contrived plasma dilution range based on the mean variant allele frequency (VAF) of the concordant somatic variants identified is generated. Using these methods, we have been able to generate sample sets for pan-cancer and disease specific evaluations. We have tested these samples through many novel high sensitivity assays that utilize both tumor-informed and tumor agnostic methods. We have confirmed that plasma-in-plasma contrived samples are amenable to all evaluated assays to date. The FFPE tumor tissue provide results matching clinical trial samples and the extraction yields of cfDNA are within the range of plasma samples from clinical trial data. Each dilution can be generated with replicates for reproducibility metrics. Current models of the sample dilutions have been generated to increase the number of replicates at relevant levels of tumor burden (i.e., 0.01% VAF). Negative samples consisting of the background plasma were also generated for each sample used. These plasma-in-plasma contrived samples have greater commutability to clinical samples than other commercial reference standards, however there are limitations. The complexity of generating these samples restrict the number of unique patients that can be utilized. Also, due to the volume of healthy plasma used as diluent, it is difficult to generate volumes greater than 4ml. To our knowledge, this is the first report examining the generation and usage of a contrived sample set that can be applied to evaluating novel high sensitivity MRD assays with clinical sample commutability. Citation Format: Paul Labrousse, Hugh Russell, David Shera, Daniel Stetson, Barrett Nuttall, Brian Dougherty, Darren Hodgson, James Hadfield. Building better contrived samples to properly evaluate Next-generation MRD and LBx assays [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5016.

Abstract 5026: Microfluidic capillary electrophoresis optimization of high-throughput cfDNA and pDNA measurements for enabling cancer diagnostics and gene therapy development

Abstract Rapid and accurate electrophoresis characterization can be an important tool for cancer researchers and therapy manufacturers. Advances in NGS of low molecular weight cfDNA for diagnostics may benefit from high-throughput checks of cfDNA sample quality with ultra-low quantities of sample. On the other hand, high molecular weight pDNA characterization and separation of supercoiled, linear and open-linear conformations aids in quality control of these payloads for personalized medicine and in particular cancer vaccines and gene therapies. This work shows optimization of established microfluidic capillary electrophoresis to enable the measurement of cfDNA and pDNA. cfDNA study was completed on plasma reformatted from whole blood tubes using Janus G3 Blood iQ workstation. The cfDNA samples were extracted using commercial cfDNA extraction kits. Using a LabChip GX Touch Biologics Characterization system: gel optimization, marker solution dilution, and inclusion of a low molecular weight DNA standard improved the sensitivity of cfDNA detection. This afforded a new electrophoresis assay with linear dynamic range of 50-1000 pg/uL and sensitivity of &amp;lt;25 ng/uL. pDNA, supercoiled DNA and linear DNA standards were prepared according to published procedures and measured on the LabChip GX Touch Biologics Characterization system. A new ladder system was developed along with gel optimization to develop a new High Sensitivity Assay platform capable of baseline resolving each conformation and providing fragment DNA sizing and purity information. Taken together, this work provides researchers new tools to leverage automated microfluidic capillary electrophoresis for DNA analysis in both upstream and manufacturing processes. Citation Format: Dipti Mehta, Gayatri Gautam, Adriana Coll de Pena, Menel Ben Frej, Anubhav Tripathi, James White. Microfluidic capillary electrophoresis optimization of high-throughput cfDNA and pDNA measurements for enabling cancer diagnostics and gene therapy development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5026.

High-sensitivity Troponin I Assay for Early Detection of Myocardial Injury in Carbon Monoxide Intoxication

Background: Carbon monoxide (CO) intoxication is the most common gas-related event resulting in emergency room (ER) visits, often leading to myocardial injuries measured through the assessment of troponin levels. Recent efforts have focused on developing high-sensitivity troponin assays for more accurate acute myocardial infarction diagnosis. However, studies using high-sensitivity troponin I (hs-TnI) assays to identify myocardial injury following CO intoxication are lacking. Aim: We compared the measurement of circulating troponin I levels using the hs-TnI assay and the contemporary troponin I (cTnI) assay. Methods: We prospectively analyzed 50 patients with CO intoxication who were admitted to the ER between September 2012 and October 2013. Clinical, demographic, electrocardiographic (ECG), echocardiographic, and laboratory data were compared. Circulating troponin I levels were measured using hs-TnI and cTnI assays upon arrival in the ER and 24, 48, and 72 h after admission. Results: Most patients with moderate or severe CO intoxication had elevated circulating troponin I levels, as detected using the hs-TnI assay. In addition, none of the results above or below the cutoff value for circulating troponin I changed from those found in the ER. In the cTnI assay, elevated circulating troponin I above the cutoff value in the ER was detected in 21 of 36 patients (58%). Participants with elevated troponin I levels, as measured by the hs-TnI assay, were more likely to experience various unfavorable clinical outcomes. Conclusion: The hs-TnI assay can detect elevated circulating troponin I levels earlier than the cTnI assay in patients with CO intoxication and myocardial injury.

Postoperative Myocardial Infarction after Non-Cardiac Surgery: An Update.

Every year, not less than 300 million non-cardiac surgery interventions are performed in the world. Perioperative mortality after non-cardiac surgery is estimated at 2% in patients over 45 years of age. Cardiovascular events account for half of these deaths, and most are due to perioperative myocardial infarction (MINS). The diagnosis of postoperative myocardial infarction, before the introduction of cardiac biomarkers, was based on symptoms and electrocardiographic changes and its incidence was largely underestimated. The incidence of MINS when a standard troponin assay is used ranges between 8 and 19% but increases to 20-30% with high-sensitivity troponin assays. Higher troponin values suggesting myocardial injury, both with or without a definite diagnosis of myocardial infarction, are associated with an increase in 30-day and 1-year mortality. Diagnostic and therapeutic strategies are reported.

Clinico Pathological Study of Rheumatoid Arthritis Association with C -Reactive Protein (CRP); a Potential Biomarker of Cartilage Damage

Objective: To explore the association between rheumatoid arthritis (RA) and C-reactive protein (CRP) levels as a potential biomarker of cartilage damage. Methodology: This case control study was done at Department of pathology Ziauddin University Clifton Campus, Karachi from June 2018 to May 2019. Patients diagnosed with rheumatoid arthritis (RA) according to established criteria, aged 18 years or older and both male and female participants were included. Clinical data was collected through medical record review and direct patient interviews. Blood samples were collected from participants for CRP measurement using standard laboratory assays. Serum CRP levels were quantified using high-sensitivity CRP assays in a certified clinical laboratory. CRP levels was defined based on established cutoff values, typically exceeding 3 mg/L. Statistical Analysis: Statistical analysis will be performed using SPSS version 26. Results: Mean age of patients was 43.38+.56 years, while control group subjects had a slightly lower mean age of 42.33+6.93 years (p = 0.412). Gender distribution showed a predominant female representation, with 76 female patients (88.4%) and 75 female controls (87.2%) (p = 0.816). There was a strong positive correlation was observed between DAS28 and CRP levels, with a Pearson correlation coefficient of r= 0.745 and (p &lt; 0.01), indicating a significant association between disease activity and CRP concentration. Conversely, the correlation between DAS28 and ESR was weaker and not statistically significant (r = 0.123, p = 0.258). Conclusion: Study revealed that the significant elevation of serum CRP levels in RA patients compared to healthy individuals. The positive correlation between serum CRP levels and the extent of joint damage observed radiographically, suggesting CRP's potential as a biomarker for estimating disease severity and cartilage deterioration in RA.

Oscillatory Hypoxia Can Induce Senescence of Adipose-Derived Mesenchymal Stromal Cells Potentiating Invasive Transformation of Breast Epithelial Cells.

Obesity is strongly associated with occurrence, metastasis, and resistance to therapy in breast cancers, which also exhibit high adipose content in the tumor microenvironment. Adipose tissue-derived mesenchymal stromal cells (ASCs) are recruited to breast cancer by many mechanisms, including hypoxia, and contribute to metastatic transition of the cancer. Breast cancers are characterized by regions of hypoxia, which can be temporally unstable owing to a mismatch between oxygen supply and consumption. Using a high-sensitivity nanopatterned stromal invasion assay, we found that ASCs could promote stromal invasion of not only breast cancer cell lines but also MCF10A1, a cell line derived from untransformed breast epithelium. RNA sequencing of MCF10A1 cells conditioned with medium from ASCs revealed upregulation of genes associated with increased cell migration, chemotaxis, and metastasis. Furthermore, we found that fluctuating or oscillating hypoxia could induce senescence in ASCs, which could result in an increased invasive potential in the treated MCF10A1 cells. These findings highlight the complex interplay within the breast cancer microenvironment, hypoxia, and the role of ASCs in transforming even non-cancerous breast epithelium toward an invasive phenotype, providing insights into early metastatic events.

Clinical Interpretation of Serum Troponin in the Era of High-Sensitivity Testing.

Cardiac troponin (Tn) plays a central role in the evaluation of patients with angina presenting with acute coronary syndrome. The advent of high-sensitivity assays has improved the analytic sensitivity and precision of serum Tn measurement, but this advancement has come at the cost of poorer specificity. The role of clinical judgment is of heightened importance because, more so than ever, the interpretation of serum Tn elevation hinges on the careful integration of findings from electrocardiographic, echocardiographic, physical exam, interview, and other imaging and laboratory data to formulate a weighted differential diagnosis. A thorough understanding of the epidemiology, mechanisms, and prognostic implications of Tn elevations in each cardiac and non-cardiac etiology allows the clinician to better distinguish between presentations of myocardial ischemia and myocardial injury-an important discernment to make, as the treatment of acute coronary syndrome is vastly different from the workup and management of myocardial injury and should be directed at the underlying cause.

Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile

BackgroundAn analytical benchmark for high-sensitivity cardiac troponin (hs-cTn) assays is to achieve a coefficient of variation (CV) of ≤ 10.0 % at the 99th percentile upper reference limit (URL) used for the diagnosis of myocardial infarction. Few prospective multicenter studies have evaluated assay imprecision and none have determined precision at the female URL which is lower than the male URL for all cardiac troponin assays. MethodsHuman serum and plasma matrix samples were constructed to yield hs-cTn concentrations near the female URLs for the Abbott, Beckman, Roche, and Siemens hs-cTn assays. These materials were sent (on dry ice) to 35 Canadian hospital laboratories (n = 64 instruments evaluated) participating in a larger clinical trial, with instructions for storage, handling, and monthly testing over one year. The mean concentration, standard deviation, and CV for each instrument type and an overall pooled CV for each manufacturer were calculated. ResultsThe CVs for all individual instruments and overall were ≤ 10.0 % for two manufacturers (Abbott CVpooled = 6.3 % and Beckman CVpooled = 7.0 %). One of four Siemens Atellica instruments yielded a CV > 10.0 % (CVpooled = 7.7 %), whereas 15 of 41 Roche instruments yielded CVs > 10.0 % at the female URL of 9 ng/L used worldwide (6 cobas e411, 1 cobas e601, 4 cobas e602, and 4 cobas e801) (CVpooled = 11.7 %). Four Roche instruments also yielded CVs > 10.0 % near the female URL of 14 ng/L used in the United States (CVpooled = 8.5 %). ConclusionsThe number of instruments achieving a CV ≤ 10.0 % at the female 99th-percentile URL varies by manufacturer and by instrument. Monitoring assay precision at the female URL is necessary for some assays to ensure optimal use of this threshold in clinical practice.

Current Evidence for the Use of High-Sensitivity Troponin Assays in the Emergency Department

Current Evidence for the Use of High-Sensitivity Troponin Assays in the Emergency Department