Biomarkers Of Failure Research Articles

Prognostic value of alveolar surfactant type-B in acute heart failure: a long-term comparative analysis vs NT-proBNP

Abstract Background In heart failure (HF) biomarkers are an integral component of prognostic assessment. Natriuretic peptides are the gold standard, but they do not directly reflect lung vascular injury. Surfactant type B (Surf-B) is released by type 2 alveolar cells under pressure induced trauma, with few reports just addressing its plasmatic levels in stable chronic HF (CHF). Information on acute HF (AHF) is lacking. Purpose To clarify the prognostic value of Surf-B changes vs NT-proBNP levels after decongestion therapy and to compare their prognostic ability at 1-year follow-up. Methods Patients with acute pulmonary edema (APE) underwent a combined evaluation of Surf-B and NT-proBNP serum levels with quantification of B-lines at hospital admission (time 0), discharge (time 1) and at 1 year (time 2). Results 54 patients (mean age 72.1 ± 11 years; mean LVEF 36% ± 13%; 65% men) were enrolled. At time 1, the average Surf-B, NT-proBNP and B-lines were significantly reduced compared to time 0 (p<0.0001). No correlation between Surf-B and NT-proBNP was observed either at time 0 (r=-0.21; p=0.12) or at time 1 (r=0.05; p=0.71). Despite the significant decrease in Surf-B levels from time 0 to time 1, 18.5% of patients behaved as non-responders exhibiting no changes in Surf-B; conversely, only 5.5% did not show significant reduction in NT-proBNP, despite significant decongestion. 38 patients were followed up to time 2: of these, 13 (34%) reached the composite endpoint of death or hospitalization for HF. Surf-B measured at time 1 was a strong predictor of adverse outcome. Patients with Surf-B above median at discharge displayed a worse survival-free from HF hospitalization compared to the remainders (Log rank p=0.012) (Figure). Also, patients with Surf-B above median at discharge had a more than 4-fold increased risk of the composite endpoint (HR 4.5, 95%CI 1.4-20.2, p=0.023). Conversely, NT-proBNP at discharge was not significantly associated with HF-free survival (Log rank p=0.26) (Figure) and was not a significant predictor of the composite outcome (HR 1.9, 95%CI 0.6-9.3, p=0.25). At ROC analysis, discharge Surf-B levels showed a higher area under the curve (AUC=0.763, p=0.011) than NT-proBNP values (AUC=0.69, p=0.063). Conclusions These data suggest that Surf-B, an organ specific biomarker of lung injury, is highly sensitive to the effectiveness of decongestion therapy, outperforming NT-proBNP. Given the high rate of patients who do not improve their Surf-B levels over time, the reparative processes of alveolar break damage may dissociate from mere decongestion and cardiac healing in AHF.Figure:1yr Kaplan-Meier survival curves

Myocardial injury and heart failure biomarkers in acute intermittent porphyria

Abstract Background Acute intermittent porphyria (AIP) is a rare metabolic disorder caused by the defect in the hydroxymethylbilane synthase gene, encoding the third enzyme in heme biosynthesis pathway. The main symptoms include abdominal pain, vomiting, paralysis, confusion. Exacerbation of AIP may manifest with elevation of blood pressure and tachycardia due to hyperactivity of sympathetic nervous system. Data regarding cardiac function in AIP are scarce. Purpose The aim of this study was to assess the myocardial injury and heart failure biomarkers during AIP exacerbations and remission. Methods This cohort prospective study encompassed patients at the age 18-65 years who had at least one exacerbation of AIP in their lifetime. Patients examined during the AIP exacerbations were reassessed in the remission phase. The concentrations of sodium, troponin T, CK-MB mass, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and metoxycatecholamines in blood were assessed. Blood pressure was measured with 24-hour ABPM. Echocardiography was performed according to the current recommendations. Results The total number of 70 patients with AIP were enrolled to the study (April 2019 - March 2023). We assessed 36 patients in both phases of disease, mean age 37 years (21-63), 75% females. The median of prior AIP exacerbations was 8. During the exacerbations a significant increase in the concentrations of NT-proBNP (250 [97 ; 501] vs. 89 [48 ; 140] pg/mL, p<0.001), metanephrine (49.0 [37.8 ; 61.2] vs. 41.4 [36.8 ; 53.3] pg/mL, p=0.009) and normetanephrine (169.8 [118.2 ; 327.2] vs. 93.2 [78.1 ; 120.9] pg/mL, p<0.001) was observed. Conversely, sodium concentrations decreased (136 [133 ; 140] vs. 140 [139 ; 142] mmol/L, p<0.001). There were no significant differences in the values of troponin (5.4 [4.0 ; 11.3] vs. 5.6 [3.7 ; 9.5] ng/L, p=0.445), CK-MB mass (1.88 [0.84 ; 2.64] vs. 1.21 [0.83 ; 2.80] ng/mL, p=0.80). In the acute phases of AIP the levels of NT-proBNP were correlated negatively with the values of sodium concentrations (r=-0.36, p=0.032) and positively with average systolic blood pressure (r=0.32, p=0.06). Echocardiography showed an increase in left ventricular (LV) mass indices in some patients hospitalized due to AIP symptoms. Sodium concentrations correlated negatively with these changes (r=-0.36, p=0.032). LV ejection fraction was slightly higher during AIP exacerbations. There were no significant differences in other parameters of LV systolic and diastolic function. Conclusions During acute intermittent porphyria (AIP) exacerbations there is an increase in the concentrations of NT-proBNP and catecholamines in blood. In most patients the levels of markers of myocardial injury, such as troponin and CK-MB mass, do not differ significantly between phases of disease. During AIP exacerbations some patients experience an increase in LV mass which may be associated with hyponatremia. In most cases cardiac function do not change significantly.Frequency of abnormal laboratory resultsResults of echocardiography

Continuous monitoring of heart failure biomarker using a sensitive graphene-based electrical sensor

Abstract Heart Failure (HF) is a complex condition that imposes significant burdens on both patients and healthcare systems. The economic impact of HF therapy and management is substantial, underscoring the urgency for proactive measures to mitigate its development. Regular assessments play a pivotal role in identifying individuals at risk and initiating timely interventions to prevent or delay HF progression [1, 2]. NT-proBNP, an amine-terminated form of brain natriuretic peptide, emerges as a promising biomarker in the realm of chronic HF diagnosis, prognosis, and risk assessment [3]. Its utility lies in providing valuable insights into disease progression and prognosis. In recent years, biosensors based on Field Effect Transistors with Graphene (Gr) gate (GFET) have garnered attention for their rapid response, sensitivity, and on-chip integration [4]. Here, we present a sensitive miniaturized GFET sensor for continuous NT-proBNP measurement. The sensor is an array of GFET devices with sensing gates of a monolayer Gr decorated with aptamers as catch probes. Averaging over similar devices in an array approach ensures measurement consistency throughout the experiment. Moreover, the significant challenge posed by the Debye length in FET biosensors is effectively addressed through the functionalization with short folding aptamers [4]. The sensor is built based on a chip comprising an array of 28 individual micro GFETs (Fig. 1a). For the functionalization of Gr gates, we utilized 1-pyrene butyric acid N-hydroxysuccinimide ester as a linker between the aptamer probes and the Gr surface. Subsequently, the Gr surface was incubated with an amine-terminated aptamer solution (Fig. 1c). A schematic diagram of the sensory chip having a droplet of the sample is shown in Fig. 1b. To quantify NT-proBNP levels an 8µL droplet of the buffer solution containing a specific NT-proBNP concentration was deposited onto the sensor. The drain current (IDS) served as the sensor signal for each target concentration (Figs. 2a and 2b). The sensor signal decreased with increasing target concentration, while negligible response was observed when injecting blank buffers. This phenomenon can be attributed to the folding of aptamers upon binding to their target. Also, continuous measurement was conducted at a fixed gate voltage of 0.9V, recording the drain current while the target concentration gradually increased in the sample droplet. This process revealed a decrease in sensor current as we expected (Fig. 2c). The sensor exhibits remarkably low detection limits of 50 pg/mL and a linear range from 100 pg/mL to 10 ng/mL, which are highly conducive for early HF diagnosis and aligning well with reported NT-proBNP levels in patient biofluid [5]. The proposed sensor holds promise as a wearable device for continuous monitoring of high-risk patients. Additionally, this technology shows potential as a detection tool for acute heart failure in hospitalized patients.Sensor viewSensor responses

Enhanced Peroxidase-like Activity of Ruthenium-Modified Single-Atom-Thick A Layers in MAX Phases for Biomedical Applications.

Nanozymes have demonstrated significant potential as promising alternatives to natural enzymes in biomedical applications. However, their lower catalytic activity compared to that of natural enzymes has limited their practical utility. Addressing this challenge necessitates the development of innovative enzymatic systems capable of achieving specific activity levels of natural enzymes. In this study, we focus on enhancing the catalytic performance of nanozymes by introducing Ru atoms into the single-atom-thick A layer of the V2SnC MAX phase, resulting in the formation of V2(Sn0.8Ru0.2)C with Ru single-atom sites. The V2(Sn0.8Ru0.2)C MAX phase demonstrated an exceptional peroxidase-like specific activity of up to 1792.6 U mg-1, surpassing the specific activity of a previously reported horseradish peroxidase (HRP). Through X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) investigations, it has been revealed that both the V2C atom layers and single-atom-thick Sn readily accept a negative charge from Ru, leading to a reduction of the energy barrier for H2O2 adsorption. This discovery has enabled the successful application of V2(Sn0.8Ru0.2)C in the development of a lateral flow immunoassay for heart failure biomarkers, achieving a detection sensitivity of 4 pg mL-1. Additionally, V2(Sn0.8Ru0.2)C demonstrated exceptional broad-spectrum antibacterial efficacy. This study lays the groundwork for the precise design of MAX phase-based nanozymes with high specific activity, offering a viable alternative to natural enzymes for various applications.

Deregulated Expression of Long Non-coding RNA ZFAS1 as a Predictive Biomarker for Respiratory Failure in Severe Pneumonia Children and Its Impact on Clinical Outcome

Abstract Objective Severe pneumonia is a common pediatric disease, often complicated by respiratory failure (RF). The expression changes of long non-coding RNA zinc finger antisense 1 (ZFAS1) were examined in children with severe pneumonia, as well as their predictive value in the occurrence of RF and poor outcomes. Methods A total of 120 children with severe pneumonia were included, 60 of whom had RF. RT-qPCR was used to detect mRNA levels. Deaths during the follow-up period were recorded through a 28-day follow-up survey. Receiver operating characteristic (ROC) curve and Kaplan Meier (K-M) plot were drawn to display diagnostic and predictive values, with the help of multiple logistic and Cox regression analysis. Results A sharp rise of serum ZFAS1 was tested in severe pneumonia children, providing a area under the receiver operator characteristic curve (AUC-ROC) of 0.920, with a sensitivity of 81.67% and a specificity of 90.00%. Serum ZFAS1 (OR = 5.832, 95% CI = 2.283–14.899) was found to be associated with the occurrence of RF after adjusting other clinical indexes, with an AUC-ROC of 0.843. ZFAS1 (HR = 4.624, 95% CI = 1.318–16.217, P < 0.05) was an independent influence factor for the poor prognosis. Cases with high ZFAS1 levels had worse clinical outcomes. Conclusion Monitoring serum ZFAS1 levels is helpful in assessing severe pneumonia in children, especially for early identification of cases with RF. High serum ZFAS1 levels have a certain predictive value for poor prognosis in patients.

Review of the potential value of serum interleukin levels as prognostic biomarkers of liver failure.

Liver failure (LF) is prevalent in China and is characterized by complex pathogenesis, challenging clinical management, poor prognosis, and rising incidence and mortality rates. The immune status is an important factor affecting LF prognosis. Interleukins (Ils) are a type of cytokine that act and interact with multiple cells, including immune cells. These signaling molecules play important roles in intercellular information transmission, including the regulation of immune cells; mediation of the activation, proliferation, and differentiation of T and B cells; and orchestration of the inflammatory response. To date, many studies have explored the correlation between IL expression and liver disease prognosis, but few studies have evaluated Ils as the prognostic biomarkers of LF. This article reviews the potential use of Ils as the prognostic biomarkers of LF. Particularly, it evaluates the predictive values of IL-21, IL-22, and IL-31, the three often overlooked yet promising prognostic biomarkers, in predicting susceptibility to LF. Harnessing biomarkers for early prognostic insights can facilitate tailored treatment strategies and enhance patient survival. Thus, this article focuses on the identification of IL-21, IL-22, and IL-33 as biomarkers in preclinical and clinical studies on LF and reviews their role as biomarkers in the pathogenesis and diagnosis of LF.

Exploring the Potential Effects and Mechanism of Astragalus Membranaceus in Treating Ischemic Heart Failure Based on Network Pharmacology and Experimental Verification.

Astragalus membranaceus (AM) is a traditional Chinese medicine that has been clinically utilized as an adjunctive therapy for the treatment of myocardial ischemia and heart failure; however, its precise molecular mechanism of action remains unknown. This study aims to investigate the potential pharmacological effects and molecular mechanism of AM in the treatment of ischemic heart failure (IHF) using network pharmacology methods, molecular docking technology, and in vitro experiments. The active components and targets of AM were obtained from the TCMSP databases, while the disease targets of IHF were retrieved from GeneCards and OMIM databases. The analysis of overlapping targets between AM and IHF mainly included active compounds-targets network, PPI network, and GO and KEGG enrichment analysis. The association between active compounds and target proteins was verified through molecular docking. Additionally, an in vitro experimental model was used to evaluate the accuracy of the forecast results. The network pharmacological analysis revealed that quercetin, kaempferol, 7-Omethylisomucronulatol, formononetin, and isorhamnetin were the core active components of AM in treating IHF. The core targets included AKT1, IL6, IL1B, PTGS2, CASP3, MMP9, and HIF1A. The molecular docking results demonstrated a strong binding affinity between these active components and targets. The KEGG pathway analysis suggested that the PI3K-AKT signaling pathway might play a central role in mediating AM's therapeutic effects on IHF. In vitro experiments demonstrated that AM treatment enhanced cell viability, reduced heart failure biomarkers, and suppressed cell apoptosis. Furthermore, the western blot analyses indicated that AM treatment effectively regulated AKT1 phosphorylation in an experimental model of IHF. Through integrated network pharmacological analysis, molecular docking technology, and in vitro experimental validation, it was demonstrated that AM can effectively mitigate IHF through activating PI3K-AKT signaling pathway. These findings significantly advance our understanding of the molecular mechanisms in IHF treatment and contribute further to promoting the clinical application of AM.

The red blood cell distribution width to albumin ratio was a potential prognostic biomarker for acute respiratory failure: a retrospective study

BackgroundThe association between red blood cell distribution width (RDW) to albumin ratio (RAR) and prognosis in patients with acute respiratory failure (ARF) admitted to the Intensive Care Unit (ICU) remains unclear. This retrospective cohort study aims to investigate this association.MethodsClinical information of ARF patients was collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) version 2.0 database. The primary outcome was, in-hospital mortality and secondary outcomes included 28-day mortality, 60-day mortality, length of hospital stay, and length of ICU stay. Cox regression models and subgroup analyses were conducted to explore the relationship between RAR and mortality.ResultsA total of 4547 patients with acute respiratory failure were enrolled, with 2277 in the low ratio group (RAR < 4.83) and 2270 in the high ratio group (RAR > = 4.83). Kaplan-Meier survival analysis demonstrated a significant difference in survival probability between the two groups. After adjusting for confounding factors, the Cox regression analysis showed that the high RAR ratio had a higher hazard ratio (HR) for in-hospital mortality (HR 1.22, 95% CI 1.07–1.40; P = 0.003), as well as for 28-day mortality and 60-day mortality. Propensity score-matched (PSM) analysis further supported the finding that high RAR was an independent risk factor for ARF.ConclusionThis study reveals that RAR is an independent risk factor for poor clinical prognosis in patients with ARF admitted to the ICU. Higher RAR levels were associated with increased in-hospital, 28-day and 60-day mortality rates.

Heart failure biomarkers and prediction of early left ventricle remodeling after acute coronary syndromes

IntroductionSeveral biomarkers are characteristically elevated in patients with acute heart failure (AHF). Our hypothesis was they could predict early changes in left ventricular (LV) characteristics in acute coronary syndrome (ACS) patients. The objective of this study was two-fold: a) compare circulating concentrations of NT-pro BNP, CA-125, ST2, galectin-3 and pro-adrenomedullin among 4 groups of individuals (healthy controls; patients with ACS without AHF; patients with ACS and AHF and patients admitted for AHF); and b) evaluate whether these biomarkers predict adverse LV remodeling and ejection fraction changes in ACS. Methods6 biomarkers (NT-pro BNP, CA-125, ST2, galectin-3, pro-adrenomedullin and C-reactive) were measured within the first 48 h of admission. Echocardiograms were performed during admission and at 3 months. Variables associated with LV end-diastolic volume (EDV) and ejection fraction (LVEF) change were assessed by multivariate linear regression. ResultsWe analyzed 51 patients with ACS, 16 with AHF and, 20 healthy controls. NT-pro BNP and ST2 concentrations were elevated at similar values in patients admitted for AHF and ACS complicated with HF but CA-125 concentrations were higher in AHF patients. NT-pro BNP concentrations were positively correlated with CA-125 (rho = 0.58; p < 0.001), ST2 (rho = 0.58; p < 0.001) and galectin-3 (rho = 0.37; p < 0.001)Median change (median days was 83 days after) in EDV and LVEF was 5 %. CA-125 concentrations were positively associated to LV EDV change (β-coefficient 1.56) and negatively with LVEF trend (β-coefficient = −0.86). No other biomarker predicted changes in EDV or LVEF. ConclusionsCA-125 correlates with early LV remodeling and LVEF deterioration in ACS patients.

Photon upconversion immunoprobe based on resonance energy transfer for brain natriuretic peptide – A prognostic biomarker for heart failure

Brain Natriuretic Peptide (BNP) holds significant clinical importance as a biomarker for heart-related conditions aiding in diagnosis, prognosis and monitoring of heart failure, providing valuable insights for timely intercession and patient management. Photon upconversion nanomaterials exhibit captivating ability to convert low energy photons to high energy ones, enabling enhanced sensitivity in sensing application. In this perspective, we develop a new photon upconversion based immunosensor for the detection of a heart failure biomarker, Brain Natriuretic Peptide (BNP) by Resonance Energy Transfer (RET) between Polyacrylic acid capped Mn2+ ions doped NaYF4:Yb/Er Upconversion Nanoparticles (PAA@Mn-NaYF4:Yb/Er UCNPs) as the donor and gold nanostar (AuNS) as the acceptor. BNP antibody was conjugated on the surface of PAA@Mn-NaYF4:Yb/Er UCNPs. The immunosensor can produce strong turn on luminescence intensity in proportional to increasing BNP antigen concentration through specific antigen–antibody interactions. The proposed photon upconversion based immunosensor can achieve turn on behaviour in the linear range from 30 pg/mL to 303 pg/mL with a Limit of Detection (LOD) of 1.76 pg/mL. The immunosensor exhibited appreciable selective and sensitive response towards BNP.

Vaginal and endometrial microbiome dysbiosis associated with adverse embryo transfer outcomes

BackgroundAssisted reproductive technology (ART) is the most effective method to treat infertility and the pathogenesis of implantation failure after in vitro fertilization-embryo transfer (IVF-ET) is a challenging filed in infertility. Microbes in the female reproductive tract are considered to be associated with gynecological and obstetric diseases. However, its effects on embryo implantation failure are unsured.PurposeThis study aimed to investigate reproductive tract dysbiosis, identify different bacteria in reproductive tract as potential biomarkers of embryo implantation failure and demonstrate the pathogenesis through metabolites analysis.MethodsWe compared the data from 16S rRNA gene and metagenome in reproductive tracts through QIIME2 and HUMAnN2 by the times of embryo implantation failure on 239 infertile patients and 17 healthy women.ResultsOur study revealed a strong positive correlation between Lactobacillus abundance and embryo implantation success (IS) after IVF-ET. The microbial community composition and structure in reproductive tract showed substantially difference between the embryo implantation failure (IF) and healthy control. Moreover, we established a diagnostic model through receiver operating characteristic (ROC) with 0.913 area under curve (AUC) in IS and multiple implantation failures (MIF), verified its effectiveness with an AUC = 0.784 demonstrating microbial community alterations could efficiently discriminate MIF patients. Metagenome functional analyses of vaginal samples from another independent infertile patients after IVF-ET revealed the L-lysine synthesis pathway enriched in IF patients, along with ascended vaginal pH and decreased Lactobacillus abundance.ConclusionsThis study clarifies several independent relationships of bacteria in vagina and endometrial fluid on embryo implantation failure and undoubtedly broadens the understanding about female reproductive health.

The Cardioprotective Potential of Herbal Formulas in Myocardial Infarction-Induced Heart Failure through Inhibition of JAK/STAT3 Signaling and Improvement of Cardiac Function.

Myocardial infarction (MI) is a leading cause of heart failure, characterized by adverse cardiac remodeling. This study evaluated the cardioprotective potential of Dohongsamul-tang (DHT), a traditional Korean herbal formula, in a rat model of MI-induced heart failure. Rats underwent left anterior descending (LAD) artery ligation and were treated with either 100 mg/kg or 200 mg/kg of DHT daily for 8 weeks. DHT treatment significantly improved cardiac function, as evidenced by increased ejection fraction (EF) from 62.1% to 70.1% (100 mg/kg) and fractional shortening (FS) from 32.3% to 39.4% (200 mg/kg) compared to the MI control group. Additionally, DHT reduced infarct size by approximately 63.3% (from 60.0% to 22.0%) and heart weight by approximately 16.7% (from 3.6 mg/g to 3.0 mg/g), and significantly decreased levels of heart failure biomarkers: LDH was reduced by 37.6% (from 1409.1 U/L to 879.1 U/L) and CK-MB by 47.6% (from 367.3 U/L to 192.5 U/L). Histological analysis revealed a reduction in left ventricle (LV) fibrosis by approximately 50% (from 24.0% to 12.0%). At the molecular level, DHT inhibited the expression of phospho-JAK by 75% (from 2-fold to 0.5-fold), phospho-STAT3 by 30.8% (from 1.3-fold to 0.9-fold), Bax/Bcl-2 by 56.3% (from 3.2-fold to 1.4-fold), and caspase-3 by 46.3% (from 1.23-fold to 0.66-fold). These results suggest that DHT exerts cardioprotective effects by modulating the JAK/STAT3 signaling pathway, highlighting its potential as a therapeutic option for heart failure.

Chemiluminescence immunoassay amplified by functional acridinium ester for the detection of NT-proBNP in clinical samples

High sensitivity and accuracy of heart failure biomarker, N-terminal prohormone brain natriuretic peptide (NT-proBNP), is critical for the early detection of heart failure. However, traditional chemiluminescent (CL) probe still face the challenges of poor solubility, in particular, significant disappointing bioavailability, which profoundly limit its clinical applications. In this paper, we demonstrate functional CL probe acridinium ester (AE-2) for the detection of NT-proBNP, through introducing a hydrophilic unit for ensuring high water dispersity and reactive group for promoting better bioavaiability with antibody. Compared to the traditional CL probe, the functional CL probe AE-2 exhibits extraordinary features, such as better biocompatibility, higher label rate with antibody, as well as significant chemiluminescence signal. In addition, this CL probe exhibits excellent linearity with the test data of Longhua Hospital, suggesting that AE-2 could be used as a clinical examination assay to detect NT-proBNP in real clinical samples. Thus, this functional CL probe AE-2 can be a powerful tool for elucidating the roles of NT-proBNP in clinical samples.

Association of velocity-pressure loop-derived values recorded during neurosurgical procedures with postoperative organ failure biomarkers: a retrospective single-center study

BackgroundPerioperative renal and myocardial protection primarily depends on preoperative prediction tools, along with intraoperative optimization of cardiac output (CO) and mean arterial pressure (MAP). We hypothesise that monitoring the intraoperative global afterload angle (GALA), a proxy of ventricular afterload derived from the velocity pressure (VP) loop, could better predict changes in postoperative biomarkers than the recommended traditional MAP and CO. MethodThis retrospective monocentric study included patients programmed for neurosurgery with continuous VP loop monitoring. Patients with hemodynamic instability were excluded. Those presenting a 1-day post-surgery increase in creatinine, B-type natriuretic peptide, or troponin Ic us were labelled Bio+, Bio− otherwise. Demographics, intra-operative data, and comorbidities were considered as covariates. The study aimed to determine if intraoperative GALA monitoring could predict early postoperative biomarker disruption. ResultFrom November 2018 to November 2020, 86 patients were analysed (Bio+/Bio− = 47/39). Bio+ patients were significantly older (62 [54−69] vs. 42 [34−57] years, p < 0.0001), More often hypertensive (25% vs. 9%, p = 0.009), and more frequently treated with antihypertensive drugs (31.9% vs. 7.7%, p = 0.013). GALA was significantly larger in Bio+ patients (40 [31−56] vs. 23 [19–29] °, p < 0.0001), while CO, MAP, and cumulative time spent <65mmHg were similar between groups. GALA exhibited strong predictive performances for postoperative biological deterioration (AUC = 0.88 [0.80−0.95]), significantly outperforming MAP (MAP AUC = 0.55 [0.43−0.68], p < 0.0001). ConclusionGALA under general anaesthesia prove more effective in detecting patients at risk of early cardiac or renal biological deterioration, compared to classical hemodynamic parameters.

An ultrasensitive nanozyme-based immunochromatographic platform for quantitative detection of NT-proBNP using V2(Sn0.8Pt0.2)C MAX phase

terminal pro-brain natriuretic peptide (NT-proBNP) has been demonstrated to be as a sensitive and specific biomarker for the heart failure (HF) management, while the development of timely and accurate point-of-care testing methods for frequent quantitative monitoring of NT-proBNP remains challenging. Nanozymes are gaining increasing attention as an alternative to natural enzymes for colorimetric lateral flow immunoassay (LFIA). However, the development of nanozymes with high catalytic activity and colorimetric signal amplification still poses challenges. Herein, we develop a novel nanozyme system with peroxidase (POD)-like activity by incorporating Pt into the A layer of V2SnC MAX phase. V2(Sn0.8Pt0.2)C MAX displays enhanced brightness in colorimetric signal and remarkably high peroxidase mimicking activity (2542.9 U mg−1), which contributes to the improvement of LFIA sensitivity through catalytic amplification. Density functional theory (DFT) calculations reveal that the presence of Pt effectively lowers the energy barrier for H2O2 adsorption at the A site in V2SnC. Specifically, V2(Sn0.8Pt0.2)C-immunolabeled LFIA strips were developed for the detection of NT-proBNP, exhibiting an unprecedented limit of detection at 0.0016 ng mL−1, which is remarkably enhanced by 1437-fold compared to conventional Au nanoparticles-based LFIA methods. Furthermore, these LFIA strips also demonstrated excellent performance in detecting human plasma-containing samples with a sensitivity of 0.02 ng mL−1 within a linear detection range of 0.02–71.64 ng mL−1. These findings suggest that V2(Sn0.8Pt0.2)C holds great potential as a signal reporter for the development of highly sensitive LFIA assays aimed at accurately monitoring HF progression and prognosis.

Elevated Serum Levels of YKL-40, YKL-39, and SI-CLP in Patients with Treatment Failure to DMARDs in Patients with Rheumatoid Arthritis.

Around 30-60% of patients with rheumatoid arthritis (RA) present treatment failure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Chitinase-like proteins (CLPs) (YKL-40, YKL-39, SI-CLP) might play a role, as they are associated with the inflammatory process. This study aimed to evaluate CLP utility as a biomarker in the treatment failure of csDMARDs. A case-control study included 175 RA patients classified into two groups based on therapeutic response according to DAS28-ESR: responders (DAS28 < 3.2); non-responders (DAS28 ≥ 3.2). CLP serum levels were determined by ELISA. Multivariable logistic regression and receiver operating characteristic (ROC) curves were used to evaluate CLPs' utility as biomarkers of treatment failure. Non-responders presented higher levels of YKL-40, YKL-39, and SI-CLP compared with responders (all: p < 0.001). YKL-40 correlated positively with YKL-39 (rho = 0.39, p < 0.001) and SI-CLP (rho = 0.23, p = 0.011) and YKL-39 with SI-CLP (rho = 0.34, p < 0.001). The addition of CLPs to the regression models improves diagnostic accuracy (AUC 0.918) compared to models including only clinical classical variables (AUC 0.806) p < 0.001. Non-responders were positive for all CLPs in 35.86%. Conclusions: CLPs could be considered as a useful biomarker to assess treatment failure, due to their association with clinical variables and improvement to the performance of regression models.

Association between dietary inflammatory index and NT-proBNP levels in US adults: A cross-sectional analysis.

With cardiovascular diseases standing as a leading cause of mortality worldwide, the interplay between diet-induced inflammation, as quantified by the Dietary Inflammatory Index (DII), and heart failure biomarker NT-proBNP has not been investigated in the general population. This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, encompassing 10,766 individuals. The relationship between the DII and NT-proBNP levels was evaluated through multivariable-adjusted regression models. To pinpoint crucial dietary components influencing NT-proBNP levels, the LASSO regression model was utilized. Stratified analyses were then conducted to examine the associations within specific subgroups to identify differential effects of the DII on NT-proBNP levels across diverse populations. In individuals without heart failure, a unit increase in the DII was significantly associated with an increase in NT-proBNP levels. Specifically, NT-proBNP levels rose by 9.69 pg/mL (95% CI: 6.47, 12.91; p < 0.001) without adjustments, 8.57 pg/mL (95% CI: 4.97, 12.17; p < 0.001) after adjusting for demographic factors, and 5.54 pg/mL (95% CI: 1.75, 9.32; p = 0.001) with further adjustments for health variables. In participants with a history of heart failure, those in the second and third DII quartile showed a trend towards higher NT-proBNP levels compared to those in the lowest quartile, with increases of 717.06 pg/mL (95% CI: 76.49-1357.63, p = 0.030) and 855.49 pg/mL (95% CI: 156.57-1554.41, p = 0.018). Significant interactions were observed in subgroup analyses by age (<50: β = 3.63, p = 0.141; 50-75: β = 18.4, p<0.001; >75: β = 56.09, p<0.001), gender (men: β = 17.82, p<0.001; women: β = 7.43, p = 0.061),hypertension (β = 25.73, p<0.001) and diabetes (β = 38.94, p<0.001). This study identified a positive correlation between the DII and NT-proBNP levels, suggesting a robust link between pro-inflammatory diets and increased heart failure biomarkers, with implications for dietary modifications in cardiovascular risk management.

Sex-based Differences in Heart Failure Biomarkers.

Differences in HF biomarker levels by sex may be due to hormonal, genetic, and fat distribution differences. Knowledge of these differences is scarce, and it is not well established whether they may affect their usefulness in the management of HF. The different biomarker profiles in women and men have been confirmed in recent studies: in women, markers of cardiac stretch and fibrosis (NP and galectin-3) are higher, whereas in men, higher levels of markers of cardiac injury and inflammation (cTn and sST2) are found. The use of new biomarkers, together with growing evidence that a multimarker approach can provide better risk stratification, raises the question of building models that incorporate sex-specific diagnostic criteria. More and more research are being devoted to understanding sex-related differences in HF. The aim of this review is to review the dynamics of HF biomarkers according to sex and in different situations, to learn whether these sex differences may affect their use in the diagnosis and follow-up of HF patients.

NT-proBNP for Predicting All-Cause Death and Heart Transplant in Children and Adults with Heart Failure.

Plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) concentration is a heart failure (HF) biomarker in adults and children. Its prognostic value for HF-related events has been established only in adults. Therefore, weaimed to test the hypothesis that plasma NT-proBNP concentrations predicted the risk of heart transplantation or death in children with HF. We studied the medical records of 109 children with HF enrolled in the IBM Watson Explorys database and from 150 children enrolled in the Pediatric Cardiomyopathy Registry (PCMR). Nonlinear regression was used to assess the relationship between plasma NT-proBNP concentrations and the risk of events in the two cohorts. All children in the PCMR cohort had dilated cardiomyopathy. The Explorys cohort also included children with congenital cardiovascular malformations. Median plasma NT-proBNP concentrations were 1250pg/mL and 184pg/mL in the Explorys and PCMR cohorts, respectively. The percentage of deaths/heart transplantations was 7%/22%, over 2years in the Explorys cohort and 3%/16% over 5years in the PCMR cohort. Mean estimates of plasma NT-proBNP concentration indicative of half-maximum relative risk for events (EC50 values) at 2 and 5years were 3730pg/mL and 4199pg/mL, respectively, values both close to the mean of 3880pg/mL established for adults with HF. The plasma NT-proBNP concentration is suitable for estimating relative risk of mortality and heart transplantation in children with HF, independent of etiology and shows similar relations to clinical outcomes as in adults, indicating its likely value as a surrogate marker both for adult and pediatric HF.ClinicalTrials.gov Identifiers: NCT00005391 (May 26, 2000), NCT01873976 (June 10, 2013).

Abstract PO3-06-01: Factors associated with first- and second- line attrition among metastatic breast cancer patients

Abstract Background: Estimating patient attrition across lines of treatment, i.e., the probability that upon failing one treatment the patient will be able to receive a subsequent treatment, may be a valuable tool for treatment sequencing. We sought to describe first-to-second line (1to2-line) and second-to third line (2to3-line) attrition rate and factors associated with attrition. Methods: The GIM14/BIO-META is an ongoing, ambispective observational multicenter study enrolling breast cancer patients receiving first-line therapy. In progressing patients, attrition was defined as no further anticancer treatment and death within 6 months from the end of the previous line. Attrition from 1to2-line and from 2to3-line was studied by descriptive analyses, factors associated with attrition by univariate ad multivariable logistic models. Results: From January 2000 to December 2021, 3,109 patients with metastatic breast cancer were enrolled in the GIM14/BIO-META study. After the exclusion of 611 patients with ongoing first-line treatment, we included 2,498 patients in the analysis of 1to2-line attrition. Considering tumor subtype, 1,650 (66.0%) patients were diagnosed with metastatic luminal-like, 622 (24.9%) with HER2-positive and 177 (7.1%) with triple negative (TN) tumors. At the time of diagnosis of advanced disease, almost half of the patients (52.0%) had only one involved metastatic site and 45.9% of the patients were diagnosed with visceral involvement. Overall, 1to2-line attrition was 9.0% (224/2,498) with similar attrition for patients with luminal-like (8.5%) and HER2-positive (7.1%) breast cancer. Patients with TN disease experience the highest 1to2-line attrition (13.0%). Age, disease-free interval from primary tumor diagnosis, and type of metastatic spread independently predicted 1to2-line attrition. Univariate analyses of factors associated with 1to2-line attrition among patients with luminal-like breast cancer were similar to those of the entire cohort. Overall, 2to3-line attrition was 14.0% (260/1,861) with higher attrition rates among patients with TN disease (22.7%) compared to patients with luminal-like (13.4%) and HER2-positive (13.0%) breast cancer. Age, tumor subtype, pattern of visceral spread and shorter time-to treatment discontinuation during first-line therapy were independent factors associated with 2to3-line attrition. Conclusions: Pending confirmation in independent series and integration with biomarkers of treatment failure, these results, may provide a valuable support for treatment decisions and clinical research on treatment sequencing. Citation Format: Eva Blondeaux, Luca Boni, Giovanna Chilà, Arianna Dri, Roberta Caputo, Francesca Poggio, Alessandra Fabi, Grazia Arpino, Federico Pravisano, Elena Geuna, Tommaso Ruelle, Irene Giannubilo, Michelino de Laurentiis, Fabio Puglisi, Claudia Bighin, Matteo Lambertini, Filippo Montemurro, Lucia Del Mastro. Factors associated with first- and second- line attrition among metastatic breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-01.