Natriuretic Peptide Precursor Research Articles

A-347 A Comprehensive Exdia TRF-LFIA for Simultaneous Quantification of GFAP and NT-proBNP in Distinguishing Ischemic and Hemorrhagic Stroke

Abstract Background The goal of this study is to create a highly sensitive time-resolved fluorescence lateral flow immunoassay (TRF-LFIA) capable of concurrently measuring glial fibrillary acidic protein (GFAP) and the N-terminal fragment of B-type natriuretic peptide precursor (NT-proBNP). This assay is designed as a diagnostic tool and aims to provide an algorithm for stroke management, specifically for distinguishing between Ischemic stroke (IS) and Hemorrhagic stroke (HS). However, LFIA to quantify simultaneous serum NT-proBNP and GFAP are not yet available. Methods We have developed and validated a novel TRF-LFIA for the simultaneous quantitative detection of NT-proBNP and GFAP. The sensitivity and reproducibility of the immunoassay were significantly improved by employing specific monoclonal antibodies linked to europium nanoparticles (EuNPs) that specifically target NT-proBNP and GFAP. The detection area on the nitrocellulose membrane featured sandwich-style complexes containing three test lines for NT-proBNP, GFAP, and Control. The fluorescence intensity of these test lines on the nitrocellulose membrane was measured using an in-house developed Exdia TRF-Plus analyzer. As proof-of-concept, we enrolled patients suspected of having a stroke who were admitted within a specific time frame (6 hours). A small amount of clinical specimen (serum) was used with a well-assembled cartridge for the measurement of GFAP and NT-proBNP. Results To optimize the LFIA, an EuNPs conjugated antibodies were investigated to improve the detection sensitivity and decrease the background signal as well shorten the detection time. The Exdia TRF-LFIA cartridge offers a wide linear dynamic detection range, rapid detection, high sensitivity, and specificity. The limit of detection was determined to be 98 pg/mL for NT-proBNP and 68 pg/mL for GFAP, with minimal cross-reactivity. There were 200 clinical human serum samples that were used to evaluate this platform with high correlation. By combining the results of NT-proBNP and GFAP, we formulated an algorithm for the clinical assessment of Ischemic Stroke (IS) and Hemorrhagic Stroke (HS). According to our proposed algorithm, the combination of GFAP and NT-proBNP emerged as the most effective biomarker combination for distinguishing between IS and HS. Conclusions Exdia TRF-LFIA shows great potential as a supplemental method for in vitro diagnostics in the laboratory or in other point-of-care testing (POCT) applications. Its development substantially decreases the diagnosis time for IS and HS. The proposed algorithm not only minimizes treatment delays but also lowers medical costs for patients.

Study on novel inflammatory indicators in marathon exercise monitoring

To analyze the changes in lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, high-sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, homocysteine, and novel inflammatory indices (neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, systemic immune-inflammation index) before and after competitions in amateur marathon runners, and to assess the effects of myocardial injury due to acute exercise and the value of novel inflammatory indices in marathon exercise monitoring. This paper is an analytical study. Amateur athletes recruited by Beijing Hospital to participate in the 2022 Beijing Marathon and the 2023 Tianjin Marathon, and those who underwent health checkups at the Beijing Hospital Medical Checkup Center from January to June 2023 were selected as the study subjects, and 65 amateur marathon runners (41 males and 24 females) and 130 healthy controls (82 males and 48 females) were enrolled in the study according to the inclusion criteria. Peripheral blood was collected one week before, immediately after, and one week after running, and routine blood tests, cardiac enzymes, infarction markers, N-terminal B-type natriuretic peptide precursor, and homocysteine were performed to calculate the values of novel inflammatory indexes. Wilcoxon signed-rank test and Spearman's rank correlation analysis were used to compare the differences in the levels of each index between the amateur marathon population and the health checkup population, and to compare the changes and correlations of each index at the three time points in the amateur marathoners.The results showed that the neutrophil-lymphocyte ratios of the healthy physical examination population and 65 amateur marathoners 1 week before running were 1.73 (1.33, 2.16) and 1.67 (1.21, 2.16), the platelet-lymphocyte ratios were 122.75 (96.69, 155.89) and 120.86 (100.74, 154.63), and the systemic immune inflammation index was 398.62 (274.50, 538.69) and 338.41 (258.62, 485.38), etc.; on 1 week before running, immediately after running and 1 week after running, lactate dehydrogenase of 65 amateur marathon runners was 173.00(159.00, 196.50)U/L,284.00(237.50, 310.50)U/L, 183.00(165.50, 206.50)U/L, creatine kinase was 131.00(94.30, 188.20)U/L,318.00(212.00, 573.15)U/L,139.00(90.55, 202.40)U/L, creatine kinase isoenzyme was 2.50(1.76, 3.43)μg/L,6.24(4.87, 10.30)μg/L,2.73(1.57, 4.40)μg/L.In 65 amateur marathon runners, lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, high sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, homocysteine, and novel inflammation markers were significantly elevated in the immediate post-run period compared with 1 week before the run, and the differences were statistically significant (Z=-7.009, Z=-6.813, Z=-6.885, Z=-7.009, Z=-7.009, Z=-6.656; P<0.05 for the above indicators).Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammatory index all showed significant positive correlation with the pre-and post-run rates of change of high-sensitivity troponin T (ρ=0.28, P=0.03;ρ=0.31, P=0.01;ρ=0.27, P=0.03); these 3 markers were also significantly and positively correlated with the pre-and post-run rates of change in a collection of myocardial-related markers such as lactate dehydrogenase, creatine kinase, creatine kinase isozymes, high-sensitivity troponin T, N-terminal B-type natriuretic peptide precursor, and homocysteine, respectively(r=0.446, P=0.039; r=0.452, P=0.033; r=0.449, P=0.036).In addition, the platelet-lymphocyte ratio was positively correlated with the pre-and post-run rates of change in creatine kinase and creatine kinase isoenzymes(ρ=0.27, P=0.03;ρ=0.28, P=0.02).In conclusion, acute myocardial injury may be triggered during marathon exercise. Changes in novel inflammatory markers were significantly associated with changes in myocardial enzymes, infarction markers, N-terminal B-type natriuretic peptide precursors, and homocysteine, which may be of value for the prediction of myocardial injury during exercise.

Clinical Characteristics of Moxifloxacin-Related Arrhythmias and Development of a Predictive Nomogram: A Case Control Study.

This study aimed to analyze the incidence, clinical characteristics, and risk factors of moxifloxacin-related arrhythmias and electrocardiographic alterations in hospitalized patients using real-world data. Concurrently, a nomogram was established and validated to provide a practical tool for prediction. Retrospective automatic monitoring of inpatients using moxifloxacin was performed in a Chinese hospital from January 1, 2017, to December 31, 2021, to obtain the incidence of drug-induced arrhythmias and electrocardiographic alterations. Propensity score matching was conducted to balance confounders and analyze clinical characteristics. Based on the risk and protective factors identified through logistic regression analysis, a prediction nomogram was developed and internally validated using the Bootstrap method. Arrhythmias and electrocardiographic alterations occurred in 265 of 21,711 cases taking moxifloxacin, with an incidence of 1.2%. Independent risk factors included medication duration (odds ratio [OR] 1.211, 95% confidence interval [CI] 1.156-1.270), concomitant use of meropenem (OR 4.977, 95% CI 2.568-9.644), aspartate aminotransferase >40 U/L (OR 3.728, 95% CI 1.800-7.721), glucose >6.1 mmol/L (OR 2.377, 95% CI 1.531-3.690), and abnormally elevated level of amino-terminal brain natriuretic peptide precursor (OR 2.908, 95% CI 1.640-5.156). Concomitant use of cardioprotective drugs (OR 0.430, 95% CI 0.220-0.841) was a protective factor. The nomogram showed good differentiation and calibration, with enhanced clinical benefit. The incidence of moxifloxacin-related arrhythmias and electrocardiographic alterations is in the range of common. The nomogram proves valuable in predicting the risk in the moxifloxacin-administered population, offering significant clinical applications.

Analysis of clinical features and prognostic factors in Takayasu arteritis involving pulmonary hypertension: A retrospective study.

Multiple takayasu arteritis (TA) is a chronic nonspecific large to medium vasculitis disease that mainly accumulates the aorta and its branches. Pulmonary vascular disease is often seen as stenosis and occlusion, and patients may show no moderate to severe pulmonary hypertension (PH). This study aims to summarize the clinical characteristics and analysis of prognostic factors in patients with PH caused by TA. Patients diagnosed with aortitis involving the pulmonary artery by pulmonary arteriography or pulmonary artery and total aortic computed tomography arteriography (CTA). All patients underwent detailed clinical assessment, laboratory data collection, and analysis of imaging data. Patients were followed up and factors affecting the prognosis of the pulmonary arteries were analyzed. Most of the patients' complaints were chest tightness, shortness of breath, decreased activity tolerance, hemoptysis and chest pain. 56.90% of the patients were in at the time of admission. Echocardiographic estimation of pulmonary artery systolic pressure was 90.39 ± 22.87 mm Hg. In terms of laboratory tests, 39.66%% of the patients had elevated C-reactive protein and erythrocyte sedimentation rate, and amino-terminal natriuretic peptide precursor on admission. In terms of imaging, all patients had pulmonary artery involvement, which was combined with aortic involvement in 31.03%. Nuclide lung perfusion/ventilation imaging of the patients revealed multiple perfusion defects/absences in the segmental and subsegmental distribution of the lungs. Univariate Cox regression model analysis suggested that patients' WHO functional class at admission, age ≧ 51 years at the time of consultation, and amino-terminal natriuretic peptide precursor ≧ 3500 pg/mL were factors affecting the prognosis. Further multifactorial Cox regression model analysis suggested amino-terminal natriuretic peptide precursor ≧ 3500 pg/mL was an independent predictor of poor prognosis with a hazard ratio (HR) value of 5.248. Electrocardiogram and echocardiogram may suggest an increased right heart load; some patients have elevated serum inflammatory indexes. Characteristic imaging manifestations include widening of the main pulmonary artery, multiple pulmonary segmental and subsegmental stenoses.

Application Value of NLR, PLR, LMR, HEART score, and POCT in Early Warning and Accurate Graded Diagnosis of High-Risk Chest Pain in Emergency Medicine

Objective: To evaluate the application value of neutrophils/lymphocytes (NLR), platelets/lymphocytes (PLR), lymphocytes/monocytes (LMR), HEART (history, electrocardiogram, age, risk factors, and troponin) score, and point-of-care testing (POCT) in the early warning and precise diagnosis of high-risk chest pain in emergency medicine. Methods: A total of 157 patients with acute chest pain who were admitted to the emergency department and chest pain treatment unit of our hospital between August 2022 and September 2023 were selected. Rapid testing of bedside myocardial markers (ultrasensitive troponin (hs-cTnI), myoglobin (MYO), creatine kinase isoenzyme (CK-MB), D-dimer (D-Dimer), and N-terminal B-type natriuretic peptide precursor (NT-proBNP)) was performed on the patients using a POCT device (ThermoKing BioMQ60proB). A HEART score was used to classify the patients into low (n = 53), intermediate (n = 59), and high-risk (n = 45) groups, and the NLR, PLR, and LMR were calculated. The NLR, PLR, and LMR values were compared among the three groups of patients, and the optimal cutoff values as well as sensitivity and specificity were determined based on receiver operating characteristic (ROC) analysis. Results: The HEART scores of patients in the low-risk, intermediate-risk, and high-risk groups were (2.72 ± 0.24), (4.75 ± 0.56), and (5.32 ± 0.73) respectively, and the differences were statistically significant (P &lt; 0.05). Compared with the low-risk group, the intermediate-risk group and high-risk group had a significantly higher NLR and PLR, and a significantly lower LMR; the high-risk group had higher NLR and PLR and lower values of LMR as compared to the other two groups, and the difference was statistically significant (P &lt; 0.05). The ROC curves suggested that the area under the curve, sensitivity, and specificity of the combined diagnosis of NLR, PLR, LMR, HEART score, and POCT were greater than those of LR, PLR, and LMR with HEART score and POCT alone. Conclusion: The combined application of NLR, PLR, LMR, HEART score, and POCT has significant application value in the early warning and precise diagnosis of emergency high-risk chest pain. It provides a more simple, easy-to-access, and efficient assessment index for the clinical prediction and treatment of emergency high-risk chest pain.

Prediction model for developing neuropsychiatric systemic lupus erythematosus in lupus patients.

This study aimed to construct a predictive model for assessing the risk of development of neuropsychiatric systemic lupus erythematosus (NPSLE) among patients with SLE based on clinical, laboratory, and meteorological data. A total of 2232 SLE patients were included and were randomly assigned into training and validation sets. Variables such as clinical and laboratory data and local meteorological data were screened by univariate and least absolute shrinkage and selection operator (LASSO) logistic regression modelling. After 10-fold cross-validation, the predictive model was built by multivariate logistic regression, and a nomogram was constructed to visualize the risk of NPSLE. The efficacy and accuracy of the model were assessed by receiver operating characteristic (ROC) curve and calibration curve analysis. Net clinical benefit was assessed by decision curve analysis. Variables that were included in the predictive model were anti-dsDNA, anti-SSA, lymphocyte count, hematocrit, erythrocyte sedimentation rate, pre-albumin, retinol binding protein, creatine kinase isoenzyme MB, Nterminal brain natriuretic peptide precursor, creatinine, indirect bilirubin, fibrinogen, hypersensitive C-reactive protein, CO, and mild contamination. The nomogram showed a broad prediction spectrum; the area under the curve (AUC) was 0.895 (0.858-0.931) for the training set and 0.849 (0.783-0.916) for the validation set. The model exhibits good predictive performance and will confer clinical benefit in NPSLE risk calculation. Key Points • Clinical, laboratory, and meteorological data were incorporated into a predictive model for neuropsychiatric systemic lupus erythematosus (NPSLE) in SLE patients. • Anti-dsDNA, anti-SSA, LYM, HCT, ESR, hsCRP, IBIL, PA, RBP, CO, Fib, NT-proBNP, Crea, CO, and mild contamination are predictors of the development of NPSLE and may have potential for research. • The nomogram has good predictive performance and clinical value and can be used to guide clinical diagnosis and treatment.

Efficacy of catheter ablation for atrial fibrillation in heart failure: a meta-analysis of randomized controlled trials.

The study aims to evaluate whether rhythm control by catheter ablation is superior to medical therapy for the patients with atrial fibrillation (AF) and heart failure (HF). The literatures were searched by using PubMed, Cochrane Library, Embase, and Web of Science databases up to 12 October 2023. The randomized controlled trials (RCTs) comparing rhythm control using catheter ablation vs. medical therapy in AF patients with HF were pooled. The primary outcomes included all-cause mortality, HF re-hospitalization, and stroke, and the secondary outcomes included left ventricular ejection fraction (LVEF), atrial tachyarrythmia recurrence, quality of life (Minnesota Living with Heart Failure Questionnaire score, MLHFQ score), 6min walking distance (6MWD), the level of N-terminal B-type natriuretic peptide precursor (NT-proBNP), and adverse events. Nine RCTs involving in 2293 patients met the inclusion criteria. Compared with medical therapy, catheter ablation reduced all-cause mortality [10.07% (121/1201) vs. 15.26% (175/1147), risk ratio (RR):0.60, 95% confidence interval (CI): 0.48-0.74, P<0.00001, I2=0%] and the rate of HF re-hospitalization (RR: 0.65, P=0.02, 95% CI: 0.45 to 0.94, I2=74%), but had no obvious difference in incidence of stroke (RR: 0.67, P=0.27, 95% CI: 0.32 to 1.38, I2=0%). Catheter ablation enhanced LVEF [mean difference (MD), 6.26%, P<0.00001, I2=89%], reduced AT recurrence (RR: 0.37, P<0.00001, 95% CI: 0.26 to 0.52, I2=89%), improved the quality of life (MLHFQ score) (MD: -6.83, P=0.003, I2=67%), elevated 6MWD (MD: 15.92, P=0.006, I2=76%), and diminished the level NT-proBNP (MD: -44.19, P<0.00001, I2=75%), but had no significant difference in adverse events [25.81% (310/1201) vs. 30.25% (347/1147), RR: 0.81, 95% CI: 0.65-1.01, P=0.06, I2=55%]. Catheter ablation as rhythm control strategy substantially enhances the survival rate, reduces HF re-hospitalization, increases the rate of sinus rhythm maintenance, improves the left ventricular function and the quality of life for AF patients with HF, and has similar safety, compared with medical therapy. The rhythm control by catheter ablation may be a better strategy for the AF patients with HF.

Arterial hypertension in the Arctic: the role of stress and autonomic dysfunction, gender differences

Introduction. Psychological stress and autonomic dysfunction are recognized as risk factors for cardiovascular diseases, but they affect cardiovascular risk differently in men and women.Aim: To study gender differences in factors influencing the probability of detecting arterial hypertension (AH) from the perspective of the role of stress, autonomic dysfunction and nonspecific inflammation in rotational shift workers in the Arctic region.Material and Methods. In the medical unit of the gas production company “Gazprom dobycha Yamburg” (polar settlement of Yamburg, 68°21’40”N) we simultaneously examined 99 men and 81 women with AH 1,2 degree of AH and normotensive persons comparable in age (p = 0.450), work experience in the Arctic (p = 0.956), number of years of rotational shift work (p = 0.824), level of office systolic (SBP) (p = 0.251) and diastolic blood pressure (DBP) (p = 0.579). Questionnaires were used to determine the level of general stress (PSM25 scale), occupational stress (Vaisman questionnaire); assessment of autonomic nervous system (ANS) function (Wayne A.M. questionnaire); 24-hour blood pressure monitoring was performed; biochemical blood test for biomarkers of inflammation, cortisol, brain natriuretic peptide precursor, homocysteine, folliclestimulating hormone was carrued out.Results. Vegetative manifestations (asthenization, increased fatigue, meteorological dependence, headaches) were significantly more often observed in women. Among men with AH, individuals with high levels of neuropsychological tension predominated, every fifth M had a high level of occupational stress. The median scores on the Wayne A.M. questionnaire were significantly higher in women, regardless of BP, and moderate ANS disorders were significantly more prevalent. According to logistic regression data, a significant effect on the probability of AH in men was the number of stress scores (OR = 1.050; 1.029–1.171, p = 0.001), indicators of nocturnal DBP variability (OR = 1.295; 1.109–1.511, p = 0.001) and nonspecific inflammation: rise in high-sensitivity C-reactive protein (hs-CRP) increased the probability of AH by 1.5 times (OR = 1.532; 1.212–1.937, p = 0.001), IL-1β – by 7 times (OR = 7.275; 3.235–16.361, p = 0.001). The probability of AH in women increased by the values of the daily variability of SBP (OR = 1.154; 1.019–1.306, p = 0.024), hs-CRP by 1.5 times (OR = 1.479; 1.226–1.783, p = 0.001), tumor necrosis factor-alpha (TNF-α) (OR = 1.111; 1.001–1.244, p = 0.044), level of IL-6 increased the probability of AH by 1.7 times (OR = 1.676; 1.149–2.958, p = 0.035), the number of scores on ANS questionnaire had a significant effect (OR = 1.055; 1.006–1.107, p = 0.026).Conclusion. In the conditions of the rotational shift work in the Arctic, gender differences were revealed in the stress perception and the severity of ANS dysfunction with a clear relationship between stress, inflammation and AH in men. ANS dysfunction in women was a trigger of nonspecific inflammation and AH. The identified gender differences will help to reveal vulnerable groups among men and women and develop targeted interventions for individuals in the Arctic region.

Visual and quantitative lateral flow immunoassay based on Au@PS SERS tags for multiplex cardiac biomarkers

Rapid and sensitive detection of multiple biomarkers by lateral flow immunoassay (LFIA) remains challenging for signal amplification for commonly used nanotags. Herein, we report a novel LFIA strip for visual and highly sensitive analysis of two cardiac biomarkers based on functionalized gold nanoparticles @ polystyrene microsphere (Au@PS）microcavity as surface-enhanced Raman scattering (SERS) tags. Antibody-modified Au@PS was designed as a SERS label. The evanescent waves propagating along the surface of the PS microcavity and the localized surface plasmons of the gold nanoparticles were coupled to enhance the light-matter interaction synergistically for Raman signal enhancement. In this strategy, the proposed Au@PS SERS tags-based LFIA was carried out to quantify the content of the heart failure and infarct biomarkers synchronously within 15 min and get the limits of detection of 1 pg/mL and 10 pg/mL for cardiac troponin I (cTnI) and N-terminal natriuretic peptide precursor (NT-proBNP), respectively. The results demonstrated 10–20 folds more sensitivity than that of the standard colloidal gold strip and fluorescent strip for the same biomarkers. This novel quantitative LFIA shows promise as a high-sensitive and visual sensing method for relevant clinical and forensic analysis.

Development and validation of a prognostic model for predicting post-discharge mortality risk in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI)

BackgroundAccurately predicting post-discharge mortality risk in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) remains a complex and critical challenge. The primary objective of this study was to develop and validate a robust risk prediction model to assess the 12-month and 24-month mortality risk in STEMI patients after hospital discharge.MethodsA retrospective study was conducted on 664 STEMI patients who underwent PPCI at Xiangtan Central Hospital Chest Pain Center between 2020 and 2022. The dataset was randomly divided into a training cohort (n = 464) and a validation cohort (n = 200) using a 7:3 ratio. The primary outcome was all-cause mortality following hospital discharge. The least absolute shrinkage and selection operator (LASSO) regression model was employed to identify the optimal predictive variables. Based on these variables, a regression model was constructed to determine the significant predictors of mortality. The performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA).ResultsThe prognostic model was developed based on the LASSO regression results and further validated using the independent validation cohort. LASSO regression identified five important predictors: age, Killip classification, B-type natriuretic peptide precursor (NTpro-BNP), left ventricular ejection fraction (LVEF), and the usage of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (ACEI/ARB/ARNI). The Harrell's concordance index (C-index) for the training and validation cohorts were 0.863 (95% CI: 0.792–0.934) and 0.888 (95% CI: 0.821–0.955), respectively. The area under the curve (AUC) for the training cohort at 12 months and 24 months was 0.785 (95% CI: 0.771–0.948) and 0.812 (95% CI: 0.772–0.940), respectively, while the corresponding values for the validation cohort were 0.864 (95% CI: 0.604–0.965) and 0.845 (95% CI: 0.705–0.951). These results confirm the stability and predictive accuracy of our model, demonstrating its reliable discriminative ability for post-discharge all-cause mortality risk. DCA analysis exhibited favorable net benefit of the nomogram.ConclusionThe developed nomogram shows potential as a tool for predicting post-discharge mortality in STEMI patients undergoing PPCI. However, its full utility awaits confirmation through broader external and temporal validation.

A comprehensive Exdia TRF-LFIA for simultaneous quantification of GFAP and NT-proBNP in distinguishing ischemic and hemorrhagic stroke

The goal of this study is to create a highly sensitive time-resolved fluorescence lateral flow immunoassay (TRF-LFIA) capable of concurrently measuring glial fibrillary acidic protein (GFAP) and the N-terminal fragment of B-type natriuretic peptide precursor (NT-proBNP). This assay is designed as a diagnostic tool and aims to provide an algorithm for stroke management, specifically for distinguishing between Ischemic stroke (IS) and Hemorrhagic stroke (HS). However, LFIA to quantify simultaneous serum NT-proBNP and GFAP are not yet available.We have developed and validated a novel TRF-LFIA for the simultaneous quantitative detection of NT-proBNP and GFAP. The sensitivity and reproducibility of the immunoassay were significantly improved by employing specific monoclonal antibodies linked to europium nanoparticles (EuNPs) that specifically target NT-proBNP and GFAP. The detection area on the nitrocellulose membrane featured sandwich-style complexes containing two test lines for NT-proBNP and GFAP, and one Control line. The fluorescence intensity of these test lines and control line was measured using an in-house developed Exdia TRF-Plus analyzer. As proof-of-concept, we enrolled patients suspected of having a stroke who were admitted within a specific time frame (6 h). A small amount of clinical specimen (serum) was used.To optimize the LFIA, an EuNPs conjugated antibodies were investigated to improve the detection sensitivity and decrease the background signal as well shorten the detection time. The Exdia TRF-LFIA cartridge offers a wide linear dynamic detection range, rapid detection, high sensitivity, and specificity. The limit of detection was determined to be 98 pg/mL for NT-proBNP and 68 pg/mL for GFAP, with minimal cross-reactivity. There were 200 clinical human serum samples that were used to evaluate this platform with high correlation. By combining the results of NT-proBNP and GFAP, we formulated an algorithm for the clinical assessment of Ischemic Stroke (IS) and Hemorrhagic Stroke (HS). According to our proposed algorithm, the combination of GFAP and NT-proBNP emerged as the most effective biomarker combination for distinguishing between IS and HS.Exdia TRF-LFIA shows great potential as a supplemental method for in vitro diagnostics in the laboratory or in other point-of-care testing (POCT) applications. Its development substantially decreases the diagnosis time for IS and HS. The proposed algorithm not only minimizes treatment delays but also lowers medical costs for patients.

Hemodynamic changes with serial balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension

Objective: To monitor hemodynamic changes during serial balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). Methods: General clinical data of CTEPH patients diagnosed from October 2017 to January 2022 in Beijing Chaoyang Hospital were collected, and 83 patients who underwent at least 1 BPA treatment were included to analyze their 6 min walking distance, WHO functional class, N-terminal B-type natriuretic peptide precursor (NT-proBNP), troponin I (cTnI) and haemodynamic indices. Baseline and follow-up after the final BPA clinical data and hemodynamics, functional status and serial hemodynamics before each series of BPA were collected to evaluate the efficacy of BPA for CTEPH patients. Complications and managements were documented to confirm the safety of BPA for CTEPH patients. Results: Three hundred and forty BPA procedures were performed in 83 CTEPH patients. The median number of BPA procedures was 4.0 and a total of 2104 vessels were dilated. In general, mPAP [from 50.0(42.0-55.25) mmHg(1 mmHg=0.133 kPa) to 32.0(27.0-42.0) mmHg, P<0.001], PVR[from (806.6±323.2) dyn·s·cm-5 to 420.0(295.0-613.5) dyn·s·cm-5, P<0.001] were significantly improved compared with baseline, but not CO and CI. Functional parameters including WHO functional class Ⅰ/Ⅱ/Ⅲ/Ⅳ (from 0/35/34/14 to 43/32/7/1, P<0.001), 6MWD [from 364.5(300.0-429.5)m to 461.0(409.0-501.0)m, P<0.001], NT-proBNP [from 1 357.0(232.0-2 715.0) ng/L to 141.0(57.0-627.8) ng/L,P<0.001] were significantly improved compared with baseline. A cumulative (compared to baseline) and serial (compared to preceding BPA session) analysis of the sequential BPA session confirmed that a major hemodynamic improvement in PVR and mPAP occurred in the first 3 serial BPA treatments. There was a dose-response relationship: the more segments that were treated, the greater were the subsequent reduction in PVR and mPAP. There were 32.0 complications (9.4%) associated with BPA procedures, and the most common complication was pulmonary hemorrhage caused by catheter-related vascular injury. Conclusions: BPA is an effective and safe alternative for technically non-operable CTEPH patients. The hemodynamic benefits of BPA in CTEPH patients were cumulative and correlated with the total number of vessels successfully dilated.

ДЕРЕВО РЕШЕНИЙ, ОПРЕДЕЛЯЮЩЕЕ ВЕРОЯТНОСТЬ УВЕЛИЧЕНИЯ СЕРДЕЧНО–СОСУДИСТОГО РИСКА У БОЛЬНЫХ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ ПОСЛЕ ВИРУСНОЙ ПНЕВМОНИИ, ВЫЗВАННОЙ SARS–COV–2

Abstract. Introduction. Recent research results demonstrate the association of arterial hypertension with the risk of infection with SARS–CoV–2, as well as with high mortality in COVID–19. An actively debated problem is the search and study of a causal relationship between a more severe COVID–19 course and the background arterial hypertension in these patients. Aim. To predict the probability of an increase in cardiovascular risk in patients with arterial hypertension within 6 months after viral pneumonia caused by SARS–COV–2, who were treated in an infectious hospital, based on constructing a decision tree using the CHAID method. Materials and Methods. A sample was formed from persons hospitalized in 2021 in an infectious hospital deployed based on the regional clinical hospital, diagnosed with “COVID–19, virus identified” (n=45). The duration of inpatient treatment was 14 [10–16] days. Among the patients included in the study, there were 22 (48,9%) women and 23 (51,1%) men. Enzyme immunoassay was used to detect the level of endothelin–1 and the N–terminal precursor of natriuretic peptide C–type in blood serum samples. Statistical analysis was carried out using the IBM SPSS Statistics 26.0 program (USA). The decision tree was constructed using the CHAID method. Results and Discussion. According to the analysis results, a statistically significant decrease in the levels of both endothelin–1 and N–terminal precursor of natriuretic peptide C–type had been detected by the time of the patients’ discharge from the hospital, as compared with their levels at admission (p&lt;0,001). The following predictors were selected for the model: Changes in the endothelin–1 levels during inpatient treatment (a decrease in the endothelin–1 level exceeding 10% was considered as positive change, while an increase in the endothelin–1 level, a retention at the same level and a decrease of less than 10% were considered as minor variation) and the level of N–terminal precursor of natriuretic peptide C–type at discharge (&gt;17,6 pg/ml and ≤17,6 pg/ml). In the resulting decision tree, 3 terminal nodes were observed. The sensitivity of the resulting model was 86.7%, while its specificity was 86,7%. The total share of correct forecasts was 86,7%. Conclusions. Determination of the levels of endothelin–1 and N–terminal precursor of natriuretic peptide C–type in the blood serum makes it possible to adequately assess and personally predict the likelihood of an increase in cardiovascular risk in patients with arterial hypertension within 6 months after viral pneumonia caused by SARS–COV–2.

Application of cardiac magnetic resonance imaging in subclinical systemic sclerosis primary heart involvement

Objectives: Primary cardiac involvement (SSc-PHI) in systemic sclerosis is an important prognostic factor. We aimed to characterize and identify subclinical SSc-PHI using cardiovascular MRI to determine whether disease severity and serum biomarkers are associated with subclinical SSc-PHI. Methods: A total of 26 patients with SSc who had no history of cardiovascular disease or pulmonary hypertension underwent 3 T-enhanced cardiovascular MRI. Measurements included native T1, extracellular volume, advanced gadolinium enhancement, T2 mapping, and left ventricular volume function. Troponin T and N telencephalic natriuretic peptide precursors were also determined. Results: LGE was observed in 13 of 26 patients (50.0%), suggesting focal fibrosis, and T2 mapping was significantly higher in the dcSSc group than in the lcSSc group (P=0.009). Left ventricular volume and function were within the normal range in all patients, but final systolic left ventricular volume was significantly higher in dcSSc than in lcSSc (P=0.021). The modified Rodnan skin score (mRSS) was significantly higher in patients with LGE focal fibrosis (P=0.019). Logistic regression analysis confirmed the association between mRSS and LGE (OR=1.224, P=0.037). In multivariate analysis, T2 mapping was negatively correlated with disease course, and was correlated with dcSSc and fingertip ulcer (R2=0.711, P=0.018, P=0.013, P=0.030). Troponin T was correlated with T2 mapping (r=0.555, P=0.049). Conclusions: Subclinical SSc-PHI is characterized by diffuse and focal myocardial fibrosis, but preserves myocardial systolic function. Subclinical SSC-Phi is associated with TNT, SSc disease severity, and complex peripheral vascular disease. These data provide information for identifying individuals at risk of SSc-PHI.

The effectiveness of hardware CPAP therapy in heart failure with preserved left ventricular ejection fraction and obstructive sleep apnea syndrome

Aim. To evaluate the effectiveness of hardware Continuous Positive Airway Pressure therapy (CPAP therapy) and its likely predictors in patients with heart failure with preserved ejection fraction (HFpEF) associated with obstructive sleep apnea syndrome (OSAS).&#x0D; Materials and methods. The study involved 207 men with HFpEF and OSAS (apnea/hypopnea index 15 per hour) who did not initially have ischemic disease and other structural heart pathology. At inclusion in the study, polysomnography and echocardiography were performed with an assessment of diastolic function and global longitudinal deformation of the left ventricular myocardium, as well as a 6-minute walk test (6MWT) and the level of the brain natriuretic peptide precursor (NT-proBNP) in the blood was determined. 80 patients received hardware CPAP the rapy, 127 patients made up the control group. After 12 months, 6MWT was repeated, NT-proBNP was determined, and clinical outcomes were assessed retrospectively.&#x0D; Results. The CPAP group had 16% fewer hospitalizations (p=0.011 [95% confidence interval – CI 4.29]) and showed a trend towards an increase in the 6MWT distance (p=0.065). To assess the likely predictors of the effectiveness of CPAP therapy, a subgroup of “responders” was identified, characterized by an increase in the distance according to the 6MWT, a decrease in the level of NT-proBNP, and the absence of adverse clinical events during the observation period. There were significant differences between responders and non-responders in apnea/hypopnea index (p=0.01 [95% CI -10.6; -2.5]), global longitudinal deformation of the left ventricular myocardium (p=0.05 [95% CI -4.7; 0]), diastolic function E/A (p=0.02 [95% CI -0.1; 0]).&#x0D; Conclusion. CPAP therapy improves clinical outcomes and functional status in patients with OSAS-associated HFpEF. The predictive model built using the identified efficacy predictors can be used to develop a personalized treatment algorithm for this cohort of patients.

Clinical characteristics, diagnosis and management of nivolumab-induced myocarditis.

Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (47.6%), and myalgias (25.4%). The levels of troponin, troponin T, troponin I, creatine kinase, creatine kinase myocardial band, creatine phosphokinase, C-reactive protein, brain natriuretic peptide, and N-terminal brain natriuretic peptide precursor were significantly increased. Histopathology often shows lymphocyte infiltration, myocardial necrosis, and fibrosis. Myocardial immunological parameters usually present positive. Cardiac imaging often suggests complete heart block, intraventricular conduction delay, arrhythmia, myocardial infarction, edema, left ventricular ejection fractions reduction, ventricular dysfunction, and other symptoms of myocarditis. Forty-two (63.6%) patients achieved remission within a median time of 8 days after discontinuation of nivolumab and treatment with systemic corticosteroids, immunoglobulins, plasmapheresis, and immunosuppressant. Thirty-five patients eventually died attributed to myocarditis (68.6%), cancer (20.0%), respiratory failure (5.7%), and other reasons (5.7%). Nivolumab-induced myocarditis should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and cardiac function imaging examinations. Nivolumab should be discontinued immediately, plasmapheresis and systemic corticosteroids combined with immunoglobulins or immunosuppressants may be an effective treatment.

Optimisation of conservative treatment of patients with severe heart failure by using hemosorption

Background. Heart failure (HF) is a complex cardiac pathology that is the main cause of hospitalisation among adults and is characterised by a high mortality. Dilated cardiomyopathy (DCM) is the most common cause of HF, and it can be fatal within a few years after the first symptoms appear. Many patients with HF remain refractory to medical therapy, despite its constant development and improvement. The study aims to compare the effectiveness of conservative treatment of patients with severe HF that occurred on the background of DCM using drug therapy and its combination with a course of hemosorption (HS). Materials and methods. We analysed treatment outcomes in 30 patients with severe HF against DCM (New York Heart Association class III–V, left ventricular ejection fraction (LV EF) &lt; 30 %). Patients in group 1 (n = 13; N-terminal fragment of brain natriuretic peptide precursor (NT-pro BNP) 4,546.23 ± ± 3,265.01 pg/ml; LV EF 16.77 ± 2.92 %; LV end-diastolic volume (EDV) 261.31 ± 60.60 ml, LV end-systolic volume (ESV) 214.85 ± 49.44 ml) received drug therapy according to local protocols. In group 2 (n = 17; NT-pro BNP 3,974.49 ± 3,550.17 pg/ml; LV EF 18.18 ± 4.36 %; LV EDV 261.12 ± 79.96 ml, LV ESV 212.06 ± 71.67 ml), medical treatment was supplemented with a course of 3 HS procedures using granular deligandizing hemosorbent. Results. Patients in both study groups noted an improvement in well-being and a decrease in the severity of symptoms. The level of NT-pro BNP decreased to 2,609.92 ± 1,465.14 pg/ml (p &lt; 0.01) in group 1 and to 975.35 ± 511.55 pg/ml (p &lt; 0.05) in group 2. LV EF increased to 22.77 ± 4.69 % and 26.76 ± 5.02 %, respectively, in the groups (p &lt; 0.01). In patients of group 1, LV EDV and LV ESV changed to 262.22 ± 40.92 ml and 211.33 ± 35.22 ml, respectively. In group 2, there was a significant decrease in LV EDV to 228.94 ± 73.16 ml and LV ESV to 170.88 ± 60.28 ml (p &lt; 0.01). Conclusions. The use of HS in combination with drug therapy for severe HF on the background of DCM improves the clinical status of patients and LV systolic function.

PATHOGENESIS OF IMMUNE DYSFUNCTION IN THE SETTING OF METABOLIK SYNDROME IN CORONARY HEAT DISEASE. QUALIFYING SCENTIFYING WORK ON THE RIGHTS OF THE MANUSCRIPT

PATHOGENESIS OF IMMUNE DYSFUNCTION IN THE SETTING OF METABOLIK SYNDROME IN CORONARY HEAT DISEASE. QUALIFYING SCENTIFYING WORK ON THE RIGHTS OF THE MANUSCRIPT

Effect of methoxymine on prevention and treatment of myocardial injury and cardiac function in elderly patients with hypotension during intraspinal anesthesia.

We aimed to investigate the effects of methoxamine to prevent hypotension in the elderly with intraspinal anesthesia (IA) on myocardial injury and cardiac function. A retrospective study was conducted by enrolling sixty elderly patients who underwent femoral head replacement (FHR) under IA in our hospital from August 2019 to August 2020. The patients were divided into two groups according to the random number table method. In the control group (CG) (30 patients), 5 mg of ephedrine was administered sedately when patients developed hypotension (20% below basal blood pressure). In the research group (RG) (30 cases), 2 μg/(kg·h) of methoxamine hydrochloride was given as a constant-rate pump before anesthesia, and 1 mg of methoxamine hydrochloride was administered intraoperatively if hypotension occurred. The hemodynamic [systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR)], myocardial injury indexes [cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), fatty acid binding protein (FABP), plasma amino-terminal brain natriuretic peptide precursor (NT-proBNP)], cardiac function indexes [systemic vascular resistance (SVR), stroke volume (SV), net percentage ejection time (ET)] were observed before anesthesia (T1), at the end of surgery (T2), and 6 h after surgery (T3) in both groups. The Bruggemann Comfort Score (BCS) and Visual Analog Scale (VAS) scores at T3, 12 h postoperatively (T4) and 24 h postoperatively (T5) in both groups were observed, and the incidence of adverse reactions to intralesional anesthesia in both groups was counted. SBP, DBP and HR at T2 were lower than those at T1 in both groups, and SBP, DBP and HR at T3 were higher than those at T2, and SBP, DBP and HR at T2 and T3 in the RG were higher than those in the CG (p<0.05). In both groups, cTnⅠ, CK-MB and FABP were higher at T2 and T3 than at T1, higher at T3 than at T2, and NT-proBNP was higher at T2 than at T1 and T3, and lower in the RG than in the CG (p<0.05). In both groups, SVR and SV at time point T2 were lower than at time point T1 and ET was higher than at time point T1, SVR and SV at time point T3 were higher than at time point T2 and ET was lower than at time point T2, SVR and SV in the RG were higher than in the CG and ET was lower than in the CG (p<0.05). VAS scores were higher in both groups at T4 and T5 than at T3, and lower in the RG than in the CG (p<0.05). Methoxamine can effectively reduce the risk of hypotension in geriatric endotracheal anesthesia, which can reduce myocardial injury and stabilize cardiac function in patients.

The state of the membrane potential of the mitochondria of blood leukocytes in acute coronary syndrome

Purpose: to assess the state of mitochondrial membrane potential of blood leukocytes in acute coronary syndrome (ACS) depending on the presence and absence of type 2 diabetes mellitus (T2DM).Material and Methods. The study involved 100 people hospitalized at the regional vascular center (RCC) of the Vladivostok Clinical Hospital No. 1 with a diagnosis of ACS, aged 35 to 65 years. The control group consisted of 30 apparently healthy volunteers of the same age and sex. At the time of admission, all patients underwent studies for the diagnosis of ACS, including an assessment of the content of troponin I (TrI), and the marker of the precursor of the cerebral natriuretic peptide (NTproBNP) and the membrane potential of mitochondria (MPM) of blood leukocytes were determined.Results. Indicators of the state MMP made it possible to assess the content of dead and living cells in the blood of the examined persons. An increase in non-viable leukocytes in the blood patients with all types of ACS, including myocardial infarction (MI) and unstable angina (UA), was established. A direct relationship was found between the increase in the number of these cells and the content of TrI in MI and a direct relationship between it and NTproBNP both in MI and NS. In patients with ACS, no significant difference was found between the MMP values of leukocytes depending on the presence of T2DM.Conclusion. An increase in the MPMP of blood leukocytes in patients accompanies of the redox balance disturbance in ACS. The established relationship between MPMP indices in MI and the content of TrI can be considered as a confirming fact of the participation of cells with mitochondrial dysfunction in the development of ischemic necrosis. The found relationship between the increase in blood leukocyte MPMP in patients with ACS and the level of NTproBNP indicates a certain contribution of mitochondrial dysfunction of leukocytes to the development of myocardial remodeling, regardless of the clinical form of ACS and the presence of DM2.