[Protective effect and mechanism of methylene blue on myocardial injury in rats with sepsis].

OBJECTIVE: To explore the protective effect of methylene blue (MB) on myocardial injury in sepsis and its possible signaling pathway. METHODS: A total of 32 female Wistar rats were randomly divided into sham operation group, sepsis model group, MB prevention group, and MB treatment group, with 8 rats in each group. The MB prevention group was injected with 15 mg/kg MB in the peritoneal cavity 6 hours before modeling; the other 3 groups were injected with 4 mL/kg saline in the peritoneal cavity. The sepsis model was established by cecal ligation puncture (CLP); the sham operation group was only subjected to an exploratory incision without ligation or puncture of the caecum. The MB treatment group was injected with 15 mg/kg MB in the peritoneal cavity 0.5 hours after modeling; the other 3 groups were injected with 4 mL/kg saline in the peritoneal cavity. Peripheral blood and myocardial tissue were collected from each group at 6 hours and 12 hours after modeling. Histological changes in the myocardial tissue were observed under the microscope; the levels of serum cardiac troponin I (cTnI), MB isoenzyme of creatine kinase (CK-MB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA); and the expressions of inducible nitric oxide synthase (iNOS), light chain 3 (LC3), and p62 in the myocardial tissue were detected by Western blotting. RESULTS: Under light microscopy, no obvious abnormalities were found in the myocardium of the sham operation group; the myocardium of the sepsis model group showed obvious inflammatory changes; the myocardium of the MB prevention group showed mild inflammatory changes at 6 hours after modeling, severe inflammatory changes at 12 hours but less severe than the sepsis model group; the myocardium of the MB treatment group showed more obvious inflammatory changes at 6 hours after modeling but less severe than the MB prevention group at 12 hours after modeling, and the inflammatory changes at 12 hours after modeling were alleviated but more severe than the 6 hours after modeling in MB prevention group. Compared with the sham operation group, the levels of cTnI, CK-MB, TNF-α and IL-6 in the MB prevention group at 6 hours and 12 hours after modeling were not significantly changed; compared with the sepsis model group, the cTnI, CK-MB, TNF-α and IL-6 levels in the MB treatment group at 6 hours and 12 hours after modeling were significantly lower [cTnI (ng/L): 175.03±12.26, 411.24±21.20 vs. 677.79±43.95 at 6 hours of modeling, 159.52±6.44, 412.46±32.94 vs. 687.61±55.09 at 12 hours of modeling; CK-MB (ng/L): 8.38±0.49, 16.87±1.41 vs. 24.87±1.74 at 6 hours of modeling, 7.94±0.30, 16.66±2.03 vs. 25.02±7.29 at 12 hours of modeling; TNF-α (ng/L): 26.98±3.31, 46.95±3.74 vs. 112.60±6.64 at 6 hours of modeling, 31.31±5.83, 90.97±5.14 vs. 149.30±4.67 at 12 hours of modeling; IL-6 (ng/L): 40.86±4.48, 128.90±3.14 vs. 248.90±12.76 at 6 hours of modeling, 80.13±7.94, 190.40±9.56 vs. 288.90±6.01 at 12 hours of modeling; all P < 0.05]. Western blotting showed that compared with the sham operation group, the protein expressions of iNOS, LC3, and p62 in the sepsis model group were significantly higher at 6 hours and 12 hours after modeling; compared with the sepsis model group, the protein expressions of iNOS, LC3, and p62 in the MB treatment group and MB prevention group were significantly lower at 6 hours and 12 hours after modeling (iNOS/GAPDH: 0.38±0.04, 0.60±0.04 vs. 0.77±0.04 at 6 hours of modeling; 0.38±0.02, 0.66±0.04 vs. 0.79±0.05 at 12 hours of modeling; LC3/GAPDH: 0.13±0.07, 0.42±0.07 vs. 1.05±0.16 at 6 hours of modeling; 0.08±0.02, 0.25±0.03 vs. 0.48±0.09 at 12 hours of modeling; p62/GAPDH: 0.17±0.05, 0.44±0.10 vs. 1.19±0.07 at 6 hours of modeling; 0.07±0.00, 0.28±0.08 vs. 0.69±0.02 at 12 hours of modeling; all P < 0.05). CONCLUSIONS: MB can reduce myocardial oxidative stress by inhibiting iNOS expression and mitochondrial autophagy in septic rats, thereby alleviating myocardial damage in sepsis, and has protective effect on myocardial damage in sepsis.

Correlation between serum cardiac troponin I level and PDAI score in patients with pemphigus vulgaris.

Pemphigus vulgaris (PV) is a rare, yet serious autoimmune disorder primarily affecting the skin and mucous membranes. While the dermatological and mucosal aspects of PV are well-documented, the potential for systemic involvement, particularly cardiac complications, remains under-explored. This study aimed to investigate the serum cardiac troponin I (cTnI) level in patients with PV versus healthy controls. The relationship between serum cardiac troponin I (cTnI) levels and various demograpgics, clinical and laboratory characteristics in patients with PV was also dealt with. This cross-sectional study was conducted on 59 patients with pemphigus vulgaris and 59 age- and sex- matched healthy controls, visited at a tertiary care hospital from August 2021 to May 2023. After thorough history taking and physical examination, troponin level was measured by the ECL (Electrochemiluminescence) method. The correlation between serum cTnI level and various variables was evaluated using Pearson's correlation coefficient. The mean serum cardiac troponin I (cTnI) level in patient group was 0.104 ± 0.05 ng/mL, with a range of 0.01 to 0.25 ng/mL. Despite mean cTnI level in patients was greater than controls, this difference was not reach to the significance level (P value: 0.058). The analysis revealed a significant positive correlation (r = 0.52, p = 0.005310), suggesting that higher PDAI scores were associated with elevated cTnI level. The correlation between serum cardiac troponin I (cTnI) level and PDAI score, even without any clinical sign or risk factor for cardiovascular disease suggests a potential link between the severity of PV and subtle cardiac involvement, highlighting the importance of cardiac monitoring in these patients.

Routine cardiac biomarkers for the prediction of incident major adverse cardiac events in patients with glomerulonephritis: a real-world analysis using a global federated database.

RATIONALE & OBJECTIVE: Glomerulonephritis (GN) is a leading cause of chronic kidney disease (CKD). Major adverse cardiovascular events (MACE) are prolific in CKD. The risk of MACE in GN cohorts is multifactorial. We investigated the prognostic significance of routine cardiac biomarkers, Troponin I and N-terminal pro-BNP (NT-proBNP) in predicting MACE within 5 years of GN diagnosis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Data were obtained from TriNetX, a global federated health research network of electronic health records (EHR). EXPOSURE OR PREDICTOR: Biomarker thresholds: Troponin I: 18 ng/L, NT-proBNP: 400 pg/mL. OUTCOMES: Primary outcome: Incidence of major adverse cardiovascular events (MACE). SECONDARY OUTCOME: was the risk for each individual component of the composite outcome. ANALYTICAL APPROACH: 1:1 propensity score matching using logistic regression. Cox proportional hazard models were used to assess the association of cardiac biomarkers with the primary and secondary outcomes, reported as Hazard Ratio (HR) and 95% confidence intervals (CI). Survival analysis was performed which estimates the probability of an outcome over a 5-year follow-up from the index event. RESULTS: Following PSM, 34,974 and 18,218 patients were analysed in the Troponin I and NTproBNP cohorts, respectively. In the Troponin I all cause GN cohort, 3,222 (9%) developed composite MACE outcome HR 1.79; (95% CI, 1.70, 1.88, p < 0.0001). In the NTproBNP GN cohort, 1,686 (9%) developed composite MACE outcome HR 1.99; (95% CI, 1.86, 2.14, p < 0.0001). LIMITATIONS: The data are derived from EHR for administrative purposes; therefore, there is the potential for data errors or missing data. CONCLUSIONS: In GN, routinely available cardiac biomarkers can predict incident MACE. The results suggest the clinical need for cardiovascular and mortality risk profiling in glomerular disease using a combination of clinical and laboratory variables.

Cardiac biomarkers as tools in the prediction and diagnosis of traumatic pericarditis and traumatic reticuloperitonitis in cattle and buffaloes.

BACKGROUND: In the livestock industry, Foreign Body Syndrome is a devastating disease condition. Feeding management, lacking of food discrimination, and eating chopped food increase the risk of swallowing sharp foreign bodies in bovine species. In addition to the honeycomb cells shape of the reticulum, the contractions of the reticular wall, gravid uterine pressure, and parturition efforts, foreign bodies can penetrate the reticular wall, causing cascade of problems including traumatic reticulitis, traumatic reticuloperitonitis, and traumatic pericarditis. The present study was carried out to evaluate the diagnostic significance of cardiac troponin I rapid test cassette and other cardiac biomarkers including serum cardiac troponin I (cTn I), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and aspartate aminotransferase enzyme (AST), in confirmed cases of traumatic pericarditis (TP) and/or traumatic reticuleoperitonitis (TRP) in cattle and buffaloes. METHODS: A total number of 30 animals (22 cattle and 8 buffaloes) with different signs such as anorexia, jugular distension, brisket edema, and signs of pain (reluctance to move, arching back, and abduction of the forelimbs) were included in the present study. Based on case history, clinical signs, ferroscopic, pericardiocentesis, radiographic and ultrasonographic examinations, TP were confirmed in cattle (n = 10) and buffaloes (n = 8) while TRP were confirmed only in cattle (n = 12). Additionally, 20 clinically healthy animals (n = 10 cattle and 10 buffaloes) were used as a control group. Blood samples were collected for determination of blood level of Tn-I, and activity of CK-MB, LDH, and AST. RESULTS: The obtained results revealed a highly significant increase in serum cTn I in diseased cattle with TP and TRP (P = 0.00), while buffaloes with TP showed no significant changes in serum cTn I (P = 0.111). Both diseased cattle and buffaloes showed increased serum activities of CK-MB, AST, and LDH enzyme. On the other hand, cardiac troponin I rapid test cassette failed to detect cTn I in diseased animals. CONCLUSION: The study concluded that the cardiac troponin I rapid test cassette did not have a diagnostic significance and could not be used as a point-of-care under field condition for diagnosis of TP and TRP in large ruminants. However, the serum troponin I level is helpful in diagnosis of TP and TRP in cattle. Although cardiac biomarkers have some diagnostic values in TP and TRP, the traditional diagnostic methods (clinical, radiography and ultrasonography examinations) are crucial for thorough evaluation of TP/TRP cases in bovine.

Possible protective effect of rosuvastatin in chemotherapy-induced cardiotoxicity in HER2 positive breast cancer patients: a randomized controlled trial.

Cardiotoxicity is a side effect of chemotherapy in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients receiving both anthracyclines and trastuzumab. We looked for a possible protective effect of rosuvastatin against chemotherapy-induced cardiotoxicity. Methods: 50 newly diagnosed HER2 positive breast cancer patients were randomly allocated into two groups: 25patients in each. Group 1(control group) received doxorubicin for 4 cycles (3 months) followed by trastuzumab adjuvant therapy. Group 2 (treatment group) received doxorubicin for 4 cycles (3 months) followed by trastuzumab adjuvant therapy and 20 mg of oral rosuvastatin 24 h before the first cycle of chemotherapy and once daily for the rest of the follow-up period (6 months). Transthoracic echocardiography was done, and blood samples were collected for patients 24 h before the initiation of therapy, after 3 months and after 6 months to assess serum levels of high sensitivity cardiac troponin I (hs-cTnI), Myeloperoxidase (MPO), Interleukin-6 (IL-6) and Alanine aminotransferase (ALT). The study was retrospectively registered in Clinical Trials.gov in April 2022. Its ID is NCT05338723. Compared to control group, Rosuvastatin-treated group had a significantly lower decline in LVEF after 3 months and after 6 months. They had significantly lower Hs-cTnI and IL-6 after 3 months and after 6 months, and significantly lower MPO after 6 months. Four patients in control group experienced cardiotoxicity while no one in rosuvastatin-treated group. Rosuvastatin attenuated cardiotoxicity, so it is a promising protective agent against chemotherapy-induced cardiotoxicity.

Comparative analysis of del Nido cardioplegia versus blood cardioplegia in isolate coronary artery bypass grafting.

BACKGROUND: This study examined the efficacy of del Nido cardioplegia compared with traditional blood cardioplegia in adult cardiac surgery for isolated coronary artery bypass grafting by evaluating the early postoperative outcomes. METHODS: A total of 119 patients who underwent isolated conventional coronary artery bypass grafting were enrolled and divided into two groups (del Nido cardioplegia group [n = 36] and blood cardioplegia group [n = 50]) based on the type of cardioplegia used. This study compared the preoperative characteristics, intraoperative data, and early postoperative outcomes. Further subgroup analyses were conducted for high-risk patient groups. RESULTS: The 30-day mortality and morbidity rates were not significantly different between groups. The del Nido cardioplegia group exhibited advantageous myocardial protection outcomes, demonstrated by a significantly smaller rise in Troponin I levels post-surgery (2.8 [-0.4; 4.2] vs. 4.5 [2.9; 7.4] ng/mL, p = 0.004) and fewer defibrillation attempts during weaning off of cardiopulmonary bypass (0.0 ± 0.2 vs. 0.4 ± 1.1 times, p = 0.011) when compared to the blood cardioplegia group. Additionally, the del Nido group achieved a reduction in surgery duration, as evidenced by the reduced aortic cross-clamping time (64.0 [55.5; 75.5] vs. 77.5 [65.0; 91.0] min, p = 0.001) and total operative time (287.5 [270.0; 305.0] vs. 315.0 [285.0; 365.0] min, p = 0.008). Subgroup analyses consistently demonstrated that the del Nido cardioplegia group had a significantly smaller postoperative increase in Troponin I levels across all subgroups (p < 0.05). CONCLUSIONS: del Nido cardioplegia provided myocardial protection and favorable early postoperative outcomes compared to blood cardioplegia, making it a viable option for conventional coronary artery bypass grafting. Establishing a consensus on the protocol for Del Nido cardioplegia administration in adult surgeries is needed.

A reagentless molecularly imprinted polymer-based electrochemical biosensor for single-step detection of troponin I in biofluids.

Reagentless molecular-imprinted polymer (MIP) electrochemical biosensors can offer the next generation of biosensing platforms for the detection of biomarkers owing to their simplicity, cost-efficacy, tunability, robustness, and accuracy. In this work, a novel combination of Prussian blue (PB), coated as an embedded redox probe on a gold working electrode (GWE), and a signal-off MIP assay has been proposed in an electrochemical format for the detection of troponin I (TnI) in biofluids. TnI is a variant exclusive to heart muscles, and its elevated level in the bloodstream is indicative of acute myocardial infarction (AMI). The proposed lab-manufactured PB/MIP electrochemical biosensor, consisting of a simple signal-off MIP assay and a PB redox probe embedded on the GWE surface, is the first of its kind that allows for reagentless, label-free, and single-step electrochemical biosensing of proteins. The preparation steps of the biosensor were fully characterized by cyclic voltammetry (CV), atomic force microscopy (AFM), and Raman spectroscopy. Finally, the performance of the optimized biosensor was investigated through the determination of various concentrations of TnI, ranging from 10 to 100 pg mL-1 within 5 min, in serum and plasma with limits of detection less than 3.6 pg mL-1, and evaluation of selectivity towards TnI using some relevant proteins that exist in biofluids with higher concentrations.

Facile, green and scalable synthesis of single-layer manganese dioxide nanosheets and its application for GSH and cTnI colorimetric detection.

Manganese dioxide (MnO2) nanosheets possess unique physical and chemical properties, making them widely applicable in various fields, such as chemistry and biomedicine. Although MnO2 nanosheets are produced using bottom-up wet chemistry synthesis methods, their scale is below the gram level and requires a long processing time, restricting their effective scale-up from laboratory to market. We report a facile, green and scalable synthesis of MnO2 nanosheets by mixing Shiranui mandarin orange juice and KMnO4 for 30 minutes. We produced more than one gram (1.095) of MnO2 nanosheets with a 0.65 nm mean thickness and a 50 nm mean lateral size. Furthermore, we established a visual colorimetric biosensing strategy based on MnO2 nanosheets for the assay of glutathione (GSH) and cardiac troponin I (cTnI), offering high sensitivity and feasibility in clinical samples. For GSH, the limit of detection was 0.08 nM, and for cTnI, it was 0.70 pg mL-1. Meanwhile, the strategy can be used for real-time analysis by applying a smartphone-enabled biosensing strategy, which can provide point-of-care testing in remote areas.

Fouling-Free electrochemical strategy based on vertically-aligned peptide layer for cardiac troponin I sensitive detection in human serum.

BACKGROUND: Cardiac troponin I (CTnI) is demonstrated as one of the most promising disease biomarkers for early diagnosing acute myocardial infarction (AMI). To date, electrochemical immunosensors have been extensively studied in the field of cTnI determination. But highly accurate and sensitive cTnI detection by this method is still a challenge due to non-specific adsorption on electrode interfaces in complex human serum. As a result, it is necessary to develop an antifouling electrochemical immunosensor with high sensitivity for the detection of cTnI. RESULTS: In this work, an antifouling electrochemical immunosensor was constructed based on vertically-aligned peptide layer consisting of Au nanoparticles (AuNPs) and amphiphilic CEAK16 peptide (CEAK16@AuNPs) for sensitive and accurate detection of cTnI in human serum. The vertically-aligned CEAK16@AuNPs interface provided a stable hydration layer originated from attraction of water molecules by amino acids on the hydrophilic side of the CEAK16, which effectively reduced non-specific adsorption and enhanced electron transfer rate. The cTnI immunosensor possessed great analytical performance with a wide range from 1 fg mL-1 to 1 µg mL-1 and a low detection limit of 0.28 fg mL-1 (S/N = 3). Additionally, the proposed CEAK16@AuNPs sensing interface showed excellent long-term antifouling performance and electrochemical activity that preserved 80 % of the initial signal after 20-days exposure in human serum samples. Consequently, the cTnI immunosensor displayed excellent detection accuracy compared to clinical methods and owned good selectivity, stability and reproducibility. SIGNIFICANCE: The development of this strategy provides a versatile tool for accurate quantitative cTnI analysis in real human serum, thus helping to achieve early AMI diagnosis effectively and holding the promising potentials for other immunosensor in disease diagnosis.

Cost-effectiveness of applying high-sensitivity troponin I to a score for cardiovascular risk prediction in asymptomatic population.

INTRODUCTION: Risk stratification scores such as the European Systematic COronary Risk Evaluation (SCORE) are used to guide individuals on cardiovascular disease (CVD) prevention. Adding high-sensitivity troponin I (hsTnI) to such risk scores has the potential to improve accuracy of CVD prediction. We investigated how applying hsTnI in addition to SCORE may impact management, outcome, and cost-effectiveness. METHODS: Characteristics of 72,190 apparently healthy individuals from the Biomarker for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project were included into a discrete-event simulation comparing two strategies for assessing CVD risk. The standard strategy reflecting current practice employed SCORE (SCORE); the alternative strategy involved adding hsTnI information for further stratifying SCORE risk categories (S-SCORE). Individuals were followed over ten years from baseline examination to CVD event, death or end of follow-up. The model tracked the occurrence of events and calculated direct costs of screening, prevention, and treatment from a European health system perspective. Cost-effectiveness was expressed as incremental cost-effectiveness ratio (ICER) in € per quality-adjusted life year (QALYs) gained during 10 years of follow-up. Outputs were validated against observed rates, and results were tested in deterministic and probabilistic sensitivity analyses. RESULTS: S-SCORE yielded a change in management for 10.0% of individuals, and a reduction in CVD events (4.85% vs. 5.38%, p<0.001) and mortality (6.80% vs. 7.04%, p<0.001). S-SCORE led to 23 (95%CI: 20-26) additional event-free years and 7 (95%CI: 5-9) additional QALYs per 1,000 subjects screened, and resulted in a relative risk reduction for CVD of 9.9% (95%CI: 7.3-13.5%) with a number needed to screen to prevent one event of 183 (95%CI: 172 to 203). S-SCORE increased costs per subject by 187€ (95%CI: 177 € to 196 €), leading to an ICER of 27,440€/QALY gained. Sensitivity analysis was performed with eligibility for treatment being the most sensitive. CONCLUSION: Adding a person's hsTnI value to SCORE can impact clinical decision making and eventually improves QALYs and is cost-effective compared to CVD prevention strategies using SCORE alone. Stratifying SCORE risk classes for hsTnI would likely offer cost-effective alternatives, particularly when targeting higher risk groups.

Protective effects of 3, 4-dihydroxybenzoic acid on myocardial infarction induced by isoproterenol in rats.

Despite considerable advances in interventions and treatment, there is a high mortality rate in patients with myocardial infarction (MI). This is the first study to investigate the protective effects of 3, 4-dihydroxybenzoic acid against isoproterenol induced MI in rats. MI was induced by isoproterenol (100-mg/kg body weight) in rats. Then, rats were treated with 3, 4-dihydroxybenzoic acid (16-mg/kg body weight) for 2 weeks. Serum creatine kinase-MB, cardiac troponin-T, cardiac troponin-I, and heart thiobarbituric acid reactive substances were significantly (p < 0.05) increased and heart superoxide dismutase and catalase activities were significantly (p < 0.05) reduced in isoproterenol-induced myocardial infarcted rats. Isoproterenol induction significantly (p < 0.05) elevated the plasma homocysteine and serum high sensitivity-C-reactive protein levels. Furthermore, an enzyme-linked immunosorbent assay, reverse transcription polymerase chain study, and immunohistochemical (IHC) staining revealed significantly (p < 0.05) elevated levels and expression of serum/myocardial nuclear factor-κB, tumor necrosis factor-alpha, interleukin-1 beta, and Interleukin-6 and significantly (p < 0.05) reduced levels/expression of serum/myocardial interleukin-10 in myocardial infarcted rats. Nevertheless, isoproterenol-induced rats treated with 3, 4-dihydroxybenzoic acid considerably (p < 0.05) attenuated all the biochemical, molecular, and IHC parameters investigated and inhibited oxidative stress and inflammation and protected the heart, through its antioxidant and anti-inflammatory mechanisms.

Barbed arrow-like structure membrane with ultra-high rectification coefficient enables ultra-fast, highly-sensitive lateral-flow assay of cTnI.

Acute myocardial infarction (AMI) has become a public health disease threatening public life safety due to its high mortality. The lateral-flow assay (LFA) of a typical cardiac biomarker, troponin I (cTnI), is essential for the timely warnings of AMI. However, it is a challenge to achieve an ultra-fast and highly-sensitive assay for cTnI (hs-cTnI) using current LFA, due to the limited performance of chromatographic membranes. Here, we propose a barbed arrow-like structure membrane (BAS Mem), which enables the unidirectional, fast flow and low-residual of liquid. The liquid is rectified through the forces generated by the sidewalls of the barbed arrow-like grooves. The rectification coefficient of liquid flow on BAS Mem is 14.5 (highest to date). Using BAS Mem to replace the conventional chromatographic membrane, we prepare batches of lateral-flow strips and achieve LFA of cTnI within 240 s, with a limit of detection of 1.97 ng mL-1. The lateral-flow strips exhibit a specificity of 100%, a sensitivity of 93.3% in detecting 25 samples of suspected AMI patients. The lateral-flow strips show great performance in providing reliable results for clinical diagnosis, with the potential to provide early warnings for AMI.

Biomarkers and prediction of anthracyclic cardiotoxicity in breast cancer.

BACKGROUND: Chemotherapy with doxorubicin may lead to left ventricular dysfunction. There is a controversial recommendation that biomarkers can predict ventricular dysfunction, which is one of the most feared manifestations of anthracycline cardiotoxicity. OBJECTIVE: The aim of this study was to evaluate the behavior of biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin in predicting cardiotoxicity in a cohort of women with breast cancer undergoing chemotherapy with anthracycline. METHODS: This is an observational, prospective, longitudinal, unicentric study, which included 40 women with breast cancer, whose therapeutic proposal included treatment with doxorubicin. The protocol had a clinical follow-up of 12 months. Biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin were measured pre-chemotherapy and after the first, third, fourth, and sixth cycles of chemotherapy. RESULTS: There was a progressive increase in type B natriuretic peptide and myoglobin values in all chemotherapy cycles. Although creatine phosphokinase fraction MB showed a sustained increase, this increase was not statistically significant. Troponin, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB were the cardiotoxicity markers with the earliest changes, with a significant increase after the first chemotherapy session. However, they were not able to predict cardiotoxicity. CONCLUSION: Troponin I, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB are elevated during chemotherapy with doxorubicin, but they were not able to predict cardiotoxicity according to established clinical and echocardiographic criteria. The incidence of subclinical cardiotoxicity resulting from the administration of doxorubicin was 12.5%.

Establishment of a microspheres-based homogeneous fluorescence immunoassay for the rapid detection of cardiac troponin I.

Myocardial infarction occurs rapidly, and thus the rapid detection of cTnI levels is the key to its diagnosis. Most current assays take 10-30 min. In this study, we developed a method for accurately measuring cardiac troponin I (cTnI) levels in human sera with amplified luminescence neighborhood homogeneous assay (AlphaLISA). The method involves coupling two cTnI antibodies targeting different epitopes to the surface of carboxylated donor and acceptor beads. The final signal values were detected by the double-antibody sandwich method, and the best reaction conditions were obtained by optimizing the experimental conditions. The sensitivity, specificity, accuracy, and precision of the method were evaluated. Results showed that the method requires only 3 min to produce the results, the detection sensitivity is 27.06 ng L-1, and the measurement range is 34.56-62 500 ng L-1. cTnI-AlphaLISA has an intra-assay precision of 2.18-4.57% (<10%) and an inter-assay precision of 5.60-6.95% (<10%). The relative recovery rates are within reasonable limits. In addition, the serum assay results of the method were compared with chemiluminescence immunoassay, and the results are in agreement with one another (ρ = 0.8803; P < 0.0001). The method is expected to be developed as a routine method, but further studies and evaluations are needed.

Homozygous TNNI3 frameshift variant in a consanguineous family with lethal infantile dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is characterized by dilatation of the left ventricle, systolic dysfunction, and normal or reduced thickness of the left ventricular wall. It is a leading cause of heart failure and cardiac death at a young age. Cases with neonatal onset DCM were correlated with severe clinical presentation and poor prognosis. A monogenic molecular etiology accounts for nearly half of cases. FAMILY DESCRIPTION: Here, we report a family with three deceased offspring at the age of 1 year old. The autopsy of the first deceased infant revealed a DCM. The second infant presented a DCM phenotype with a severely reduced Left Ventricular Ejection Fraction (LVEF) of 10%. Similarly, the third infant showed a severe DCM phenotype with LVEF of 30% as well, in addition to eccentric mitral insufficiency. RESULTS: Exome sequencing was performed for the trio (the second deceased infant and her parents). Data analysis following the autosomal dominant and recessive patterns of inheritance was carried out along with a mitochondrial pathways-based analysis. We identified a homozygous frameshift variant in the TNNI3 gene (c.204delG; p.(Arg69AlafsTer8)). This variant has been recently reported in the ClinVar database in association with cardiac phenotypes as pathogenic or likely pathogenic and classified as pathogenic according to ACMG. CONCLUSION: Genetic counseling was provided for the family and a prenatal diagnosis of choronic villus was proposed in the absence of pre-implantation genetic diagnosis possibilities. Our study expands the case series of early-onset DCM patients with a protein-truncating variant in the TNNI3 gene by reporting three affected infant siblings.

Elevated Cardiac Troponin I as a Mortality Predictor in Hospitalised COVID-19 Patients.

Background and Objectives: SARS-CoV-2 affects multiple organ systems, including the cardiovascular system, leading to immediate and long-term cardiovascular complications. Acute myocardial injury is one of the earliest and most common cardiac issues in the acute phase of COVID-19. This study aimed to evaluate the prognostic value of cardiac troponin I (cTnI) levels in predicting in-hospital mortality among hospitalised COVID-19 patients. Materials and Methods: A retrospective observational cohort study included 2019 adult patients hospitalised with a confirmed COVID-19 infection stratified by cTnI levels on admission into three groups: <19 ng/L (1416 patients), 19-100 ng/L (431 patients), and >100 ng/L (172 patients). Myocardial injury was defined as blood serum cTnI levels increased above the 99th percentile upper reference limit. Depersonalised datasets were extracted from digital health records. Statistical analysis included multivariable binary logistic and Cox proportional hazards regressions. Results: Overall, 29.87% of patients experienced acute myocardial injury, which development was associated with age, male sex, chronic heart failure, arterial hypertension, obesity, and chronic kidney disease. Among patients with cTnI levels of 19-100 ng/L, the odds ratio for requiring invasive mechanical ventilation was 3.18 (95% CI 2.11-4.79) and, for those with cTnI > 100 ng/L, 5.38 (95% CI 3.26-8.88). The hazard ratio for in-hospital mortality for patients with cTnI levels of 19-100 ng/L was 2.58 (95% CI 1.83-3.62) and, for those with cTnI > 100 ng/L, 2.97 (95% CI 2.01-4.39) compared to patients with normal cTnI levels. Conclusions: Increased cardiac troponin I, indicating myocardial injury, on admission is associated with a more adverse clinical disease course, including a higher likelihood of requiring invasive mechanical ventilation and increased risk of in-hospital mortality. This indicates cardiac troponin I to be a beneficial biomarker for clinicians trying to identify high-risk COVID-19 patients, choosing the optimal monitoring and treatment strategy for these patients.

Versatile conductometric biosensors for rapid and selective detection of inflammatory and cardiac biomarkers in saliva.

Biosensors have become promising alternatives to the conventional methods in early identification of diseases. However, translation of biosensors from lab to commercial products have challenges such as complex sensor fabrications and complicated detection, and inadequate sensitivity and selectivity. Here, we introduce simple and low-cost fabricated conductometric sensors based on high resistivity silicon wafers (HR-Si) which can be adopted to functionalise with both natural and synthetic antibodies in detecting five biomarkers including interleukin-6, C reactive protein, cardiac troponin I, brain natriuretic peptide, and N terminal-probrain natriuretic peptide. All five biomarkers show selective and rapid (10 min sample incubation and <1 min of reading time) detection in both media of phosphate buffer saline and saliva with the detection limits lower than that of reported healthy levels in saliva. This work highlights the versatility of HR-Si sensors in functionalisation of both natural and synthetic antibodies in sensitive and selective biomarker detection. As these miniaturised conductometric biosensors can be easily modified with on-demand biomaterials to detect corresponding target biomarkers, they enable a new category of compact point-of-care medical devices.

Ckip-1 3'UTR alleviates prolonged sleep deprivation induced cardiac dysfunction by activating CaMKK2/AMPK/cTNI pathway.

Sleep deprivation (SD) has emerged as a critical concern impacting human health, leading to significant damage to the cardiovascular system. However, the underlying mechanisms are still unclear, and the development of targeted drugs is lagging. Here, we used mice to explore the effects of prolonged SD on cardiac structure and function. Echocardiography analysis revealed that cardiac function was significantly decreased in mice after five weeks of SD. Real-time quantitative PCR (RT-q-PCR) and Masson staining analysis showed that cardiac remodeling marker gene Anp (atrial natriuretic peptide) and fibrosis were increased, Elisa assay of serum showed that the levels of creatine kinase (CK), creatine kinase-MB (CK-MB), ANP, brain natriuretic peptide (BNP) and cardiac troponin T (cTn-T) were increased after SD, suggesting that cardiac remodeling and injury occurred. Transcript sequencing analysis indicated that genes involved in the regulation of calcium signaling pathway, dilated cardiomyopathy, and cardiac muscle contraction were changed after SD. Accordingly, Western blotting analysis demonstrated that the cardiac-contraction associated CaMKK2/AMPK/cTNI pathway was inhibited. Since our preliminary research has confirmed the vital role of Casein Kinase-2 -Interacting Protein-1 (CKIP-1, also known as PLEKHO1) in cardiac remodeling regulation. Here, we found the levels of the 3' untranslated region of Ckip-1 (Ckip-1 3'UTR) decreased, while the coding sequence of Ckip-1 (Ckip-1 CDS) remained unchanged after SD. Significantly, adenovirus-mediated overexpression of Ckip-1 3'UTR alleviated SD-induced cardiac dysfunction and remodeling by activating CaMKK2/AMPK/cTNI pathway, which proposed the therapeutic potential of Ckip-1 3'UTR in treating SD-induced heart disease.

The impact of obesity, age, and gender on plasmatic levels of selected glycoprotein biomarkers and miRNA-499 in OSA patients.

BACKGROUND: The current obstructive sleep apnea (OSA) diagnostic uses polysomnography or limited polygraphy and requires specialized personnel and technical equipment. Glycoprotein biomarkers and microRNAs are being explored as a possible new method for screening. We aimed to evaluate whether certain biomarkers and microRNA, previously identified as related to OSA, could be influenced by factors such as gender, age, and obesity level in patients with OSA. METHODS: In this retrospective analytical study, patients with moderate to severe OSA (n = 130) were compared with the control group. Serum levels of selected biomarkers and microRNA were taken from both groups. The group of OSA patients was then stratified by gender, obesity level, and age to see the possible influence of those variables on biomarker levels. RESULTS: Levels of all studied biomarkers - C-reactive protein (CRP), high-sensitivity troponin I (hsTnI), pentraxin-3 (PTX-3), and microRNA-499 were significantly higher in patients with OSA compared to the control group. In the OSA group only hsTnI showed a statistically significant relationship with gender. Levels of CRP and hsTnI showed a significant dependence on the level of obesity. Dependency on age was proven for hsTnI. CRP, PTX-3, and microRNA-499 did not have any statistically significant relationship with age. CONCLUSION: We found that serum levels of pentraxin-3 and microRNA-499 in patients with moderate to severe obstructive sleep apnoea are independent of gender, obesity, and age. CRP was affected by the level of obesity and hsTnI was influenced by all 3 variables. We consider these findings important for further research of OSA biomarkers.

External validation of the myocardial-ischaemic-injury-index machine learning algorithm for the early diagnosis of myocardial infarction: a multicentre cohort study.

BACKGROUND: The myocardial-ischaemic-injury-index (MI3) is a novel machine learning algorithm for the early diagnosis of type 1 non-ST-segment elevation myocardial infarction (NSTEMI). The performance of MI3, both when using early serial blood draws (eg, at 1 h or 2 h) and in direct comparison with guideline-recommended algorithms, remains unknown. Our aim was to externally validate MI3 and compare its performance with that of the European Society of Cardiology (ESC) 0/1h-algorithm. METHODS: In this secondary analysis of a multicentre international diagnostic cohort study, adult patients (age >18 years) presenting to the emergency department with symptoms suggestive of myocardial infarction were prospectively enrolled from April 21, 2006, to Feb 27, 2019 in 12 centres from five European countries (Switzerland, Spain, Italy, Poland, and Czech Republic). Patients were excluded if they presented with ST-segment-elevation myocardial infarction, did not have at least two serial high-sensitivity cardiac troponin I (hs-cTnI) measurements, or if the final diagnosis remained unclear. The final diagnosis was centrally adjudicated by two independent cardiologists using all available medical records, including serial hs-cTnI measurements and cardiac imaging. The primary outcome was type 1 NSTEMI. The performance of MI3 was directly compared with that of the ESC 0/1h-algorithm. FINDINGS: Among 6487 patients, (median age 61·0 years [IQR 49·0-73·0]; 2122 [33%] female and 4365 [67%] male), 882 (13·6%) patients had type 1 NSTEMI. The median time difference between the first and second hs-cTnI measurement was 60·0 mins (IQR 57·0-70·0). MI3 performance was very good, with an area under the receiver-operating-characteristic curve of 0·961 (95% CI 0·957 to 0·965) and a good overall calibration (intercept -0·09 [-0·2 to 0·02]; slope 1·02 [0·97 to 1·08]). The originally defined MI3 score of less than 1·6 identified 4186 (64·5%) patients as low probability of having a type 1 NSTEMI (sensitivity 99·1% [95% CI 98·2 to 99·5]; negative predictive value [NPV] 99·8% [95% CI 99·6 to 99·9]) and an MI3 score of 49·7 or more identified 915 (14·1%) patients as high probability of having a type 1 NSTEMI (specificity 95·0% [94·3 to 95·5]; positive predictive value [PPV] 69·1% [66·0-72·0]). The sensitivity and NPV of the ESC 0/1h-algorithm were higher than that of MI3 (difference for sensitivity 0·88% [0·19 to 1·60], p=0·0082; difference for NPV 0·18% [0·05 to 0·32], p=0·016), and the rule-out efficacy was higher for MI3 (11% difference, p<0·0001). Specificity and PPV for MI3 were superior (difference for specificity 3·80% [3·24 to 4·36], p<0·0001; difference for PPV 7·84% [5·86 to 9·97], p<0·0001), and the rule-in efficacy was higher for the ESC 0/1h-algorithm (5·4% difference, p<0·0001). INTERPRETATION: MI3 performs very well in diagnosing type 1 NSTEMI, demonstrating comparability to the ESC 0/1h-algorithm in an emergency department setting when using early serial blood draws. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, the EU, the University Hospital Basel, the University of Basel, Abbott, Beckman Coulter, Roche, Idorsia, Ortho Clinical Diagnostics, Quidel, Siemens, and Singulex.