Risultati per: Scoperto nuovo biomarker per il cancro al colon-retto

La Presidenza del Consiglio aderisce a ‘Illumina novembre’

Introduction
Early detection of colorectal cancer (CRC) and clinically relevant (advanced) adenomas leads to a significant reduction of CRC-related mortality and morbidity. However, the faecal immunochemical test (FIT) suffers from a high number of false-positive results and is insensitive to detecting advanced adenomas, resulting in false-negative results for these premalignant lesions. Therefore, more accurate, non-invasive screening tools are needed for the detection and prognostication of colorectal neoplasia. Previous research on volatile organic compounds (VOCs) analysis in breath and faeces has shown to be promising potential biomarkers for this purpose. Several VOC-sampling methods, including breath sampling, have improved significantly over the recent years resulting in an increased reliability of measurements. Therefore, we aim to identify relevant VOC profiles in exhaled breath and faeces for the diagnosis of colorectal neoplasia while taking into account relevant confounding factors. Follow-up data will be used to identify relevant VOC profiles in exhaled breath and faeces for the prognostication of colorectal neoplasia. Finally, a biobank will be set up for future research questions on this topic.

Methods and analysis
Subjects with positive FIT within the Dutch national CRC cancer screening programme are included. Subjects are asked to fill in questionnaires and exhaled breath, faeces and blood are sampled prior to colonoscopy. All subjects are asked to fill in follow-up questionnaires at years 1 and 5 of the study. In case of surveillance colonoscopies, subjects are asked to provide exhaled breath, faeces and blood prior to the colonoscopy again. Breath sampling is performed using the ReCIVA breath sampler. VOCs in breath and faeces are analysed using gas-chromatography-mass spectrometry (GC-MS). Raw GC-MS data is preprocessed and analysed using machine learning techniques.

Ethics and dissemination
The study is approved by the medical ethics committee at the Maastricht University Medical Center (NL74844.068.20) in November 2021 and started inclusion in January 2022.

Circulation, Volume 150, Issue Suppl_1, Page A4123631-A4123631, November 12, 2024. Background:Right ventricular failure is a major prognostic determinant of pulmonary hypertension and progresses with myocardial fibrosis. Extracellular matrix proteins play a major role in myocardial fibrosis. Right ventricular biomarkers for right ventricular function and fibrosis are poorly examined in pulmonary hypertension. This study investigated the significance of collagen triple helix repeat-containing protein 1 (CTHRC1), one of the extracellular matrix proteins, as a right ventricular biomarker.Methods and Results:A monocrotaline-induced pulmonary hypertension rat model was used in this study. CTHRC1 expression in the right ventricle was higher in rats with monocrotaline-induced pulmonary hypertension than in controls. CTHRC1 was associated with fibrosis in the rat’s right ventricle. Next, human circulating CTHRC1 levels were evaluated in controls (n = 20), pulmonary arterial hypertension (PAH, n = 46), and chronic thromboembolic pulmonary hypertension (CTEPH) patients (n = 64). Human circulating CTHRC1 levels were higher in PAH (P = 0.006) and CTEPH patients (P = 0.011) than in controls (Figure). Human circulating CTHRC levels were correlated with tricuspid lateral annular peak systolic velocity (R = -0.213, P = 0.029), right ventricular fractional area change (R = -0.225, P = 0.017), and right ventricular global longitudinal strain evaluated by magnetic resonance imaging (R = 0.429, P = 0.009). In addition, human circulating CTHRC1 levels were decreased after balloon pulmonary angioplasty (P < 0.001) in CTEPH patients.Conclusions:CTHRC1 could be a novel biomarker associated with right ventricular failure and fibrosis in pulmonary hypertension patients.

Circulation, Volume 150, Issue Suppl_1, Page A4144529-A4144529, November 12, 2024. Introduction:Cardiac hypertrophy is a known adverse prognostic marker in various non-transplant pathologies. In heart transplant patients, due to many confounders, it has been controversial on the relevance and timing of cardiac hypertrophy as an adverse remodeling vs acute injury pattern in an immunologically hostile environment. Previous studies have shown prognostication of hypertrophy on echocardiogram at 1-year post-heart transplant.Research Questions:Does cardiac hypertrophy within a year after transplant have long-term prognostic implications?Methods:We collected relevant clinical variables for all heart transplants using EPIC EHR’s Clarity database. Hypertrophy was defined based on LV Mass Indexed to body surface area where LV Mass = 0.8 x (1.04 x (((LVIDD + IVSd + PWd)3- LVIDD3))) + 0.6. Relative Wall Thickness was defined as RWT = 2 x PWd / LVIDD. We used a rule-based natural language processing program validated by correlation with manual readings by trained cardiologists (r=0.96, p=0.007) to abstract echo variables.Results:Inclusion criteria were heart transplants performed from 2015 to 2023 at our center, with an echocardiogram closest to 6 months (+/- 1 month). Ten percent (n=33) showed hypertrophy on echocardiograms at 6 months (Table 1). Of these, 20 (61%) had mild, 3 (9%) severe, and 10 (30%) moderate hypertrophy. Of 33 patients, 28 (85%) had concentric, and 5 (15%) had eccentric hypertrophy. Patients with hypertrophy at 6 months had significantly worse survival at 5 years (p=0.01) and 10 years (p=0.05) compared to patients without hypertrophy (Fig 1). Survival at 5 and 10 years was not statistically different for patients with hypertrophy at 3 months (5 yrs p=0.17, 10 yrs p=0.06), 12 months (5 yrs p=0.38, 10 yrs p=0.30), and 18 months (5 yrs p=0.15, 10 yrs p=0.08) compared to those without hypertrophy.Conclusion:Cardiac hypertrophy on echocardiogram at 6 months predicts adverse long-term survival, while other time points did not.

Circulation, Volume 150, Issue Suppl_1, Page A4141403-A4141403, November 12, 2024. Background:Two-dimensional speckle tracking echocardiographic (2D-STE) strain analysis is modern and inovatively useful in overcoming technical echocardiographic limitations. To-date no larger studies have assessed sub-clinical myocardial mechanics in acute tuberculous pericarditis (ATBP) and age/sex/ethnic differences, and synergistic-prognostic association of these parameters with patients’ outcomes (survival).Aim:To assess the prognostic relation between age/sex/ethnitic differences with right (RV) and left (LV) ventricular systolic and diastolic strain (and other parameters/biomarkers) with outcome ATBP and preserved LV function.Methods and results:A total of 362 (mean age 37years, LVEF 56%, 57% males) consecutive patients with ATBP were enrolled and subseguently had 2D-STE strain analysis performed on their the 2D-TTE images. Sex, age and ethnic differences were assessd and all were prospectively followed for new CVS eventsincluding new onset acute heart failure or deterioration in LV function, hospitalization for HF, CVS-related death, recurrent effusion or tamponade.The LV and RV longitudinal strain parameters were assessed using the 2D-STE. Of the 362 patients eligible for the study, 142 developed 84 new CVS-related events during a mean follow-up of 12 ±6 months. The RV free-wall, global RV and LV systolic and diastolic strain parameters, elevated NT Pro-BNP and troponins, RV fractional area change, low TAPSE, LV end-diastolic volume, LA volume index, moderate TR, and mPASP > 40mmHg were independently predictive of combined outcomes (p LV strain parameters and best performance predictive of CVS events was greatest for RV compared with LV strain. There was a stronger association between the degree of RV dysfunction and risk of CVS events for RV free wall- and global systolic and diastolic strain parameters and biomarker compared with LV strain parameters.Male sex, older age (at least 42years) and black etnicity were further independent risk factors of outcomes.Conclusion:Patients with ATBP and normal LVEF, and myocardial mechanical dysfunction in addition to elevated biomarkers were stronger predictors of outcome more so for those with RV dysfuntion than other conventional and LV mechanical parameters. Male sex, older age and black ethnicity provided additional independent risk of outcomes in ATBP,providing stronger prognostic stratification.

Circulation, Volume 150, Issue Suppl_1, Page A4138019-A4138019, November 12, 2024. Background:We recently determined that cellular communication network factor 2 (CCN2) (also known as IGFBP8) levels associate with metrics of severity, and survival, in pulmonary arterial hypertension (PAH). While genetic variants that modify CCN2 gene expression have been described, the variants across the genome that associate with CCN2 protein levels in human circulation remain unknown.Research Question:We sought to identify genetic variants associated with circulating levels of CCN2 and to determine those variants’ relationship with clinical severity and survival.Methods:Serum CCN2 was measured by ELISA in subjects from a national sample repository, the PAH Biobank. A genome wide association study (GWAS) for CCN2 (natural log transformed) was performed in White idiopathic PAH (IPAH) PAH Biobank participants (n = 768) using Illumina OMNI5 genotypes in plink after standard quality control. Subsequent exploration of the SNP of interest was conducted in a separate dataset of 687 White PAH participants (n=360 IPAH, n=313 APAH) linked to genetic and clinical data, including REVEAL 2.0 risk score assessment (divided into low, medium, and high-risk levels) and outcomes (the STRIDE (Sitaxsentan To Relieve Impaired Exercise) trials cohort).Results:In the PAH Biobank, using GWAS, we found CCN2 levels were significantly associated with rs9493157 (p = 2.8 x10-12) (Figure A). rs9493157 is reported in the Genotype-Tissue Expression (GTEx) portal to be an eQTL for CCN2 expression in the left ventricle. In the STRIDE cohort, the hazard ratio (HR) for death was 1.33 (99% CI 1.03 to 1.72) for participants with one or more T alleles (p=0.027; (Figure B)). On multivariate analysis, the HR for death was 1.28 (95% CI 0.99 to 1.66; p=0.060). Among subjects with the highest REVEAL2.0 risk, those with a T allele had worse survival than those no T allele, with best survival among those with low a REVEAL2.0 score and no T allele.Conclusions:In White PAH subjects, rs9493157 associates with human levels of serum CCN2, a known biomarker for PAH. While additional studies are warranted, the T allele associates with worse survival and may enhance the prognostic value of the REVEAL2.0 risk score.

Circulation, Volume 150, Issue Suppl_1, Page A4144785-A4144785, November 12, 2024. Background:Acquired mitochondrial dysfunction is one of the characteristics of pulmonary arterial hypertension (PAH). Exploring potential biomarkers from mitochondrial perspective may be effective in the diagnosis and treatment of PAH. We aimed to screen for potential mitochondria-related biomarker(s) associated with PAH using integrated bioinformatics approach and machine learning algorithms.Methods:On the basis of gene expression profiles of PAH and healthy samples from the GEO database, hub differentially expressed mitochondrial genes were identified Integrated machine learning algorithm and bioinformatics analysis were performed, including functional enrichment analysis, consensus clustering, and weighted gene co-expression network analysis. Then, the potential biomarkers for PAH were accessed by single-cell data analysis, drug prediction, miRNA-transcription factor-mRNA network construction, and receiver operating characteristic curves. Finally, we explored the associations between the hub mitochondrial genes and immune cell infiltration.Results:One hub mitochondria gene ARMCX3 was identified. ARMCX3 has strong stability and high accuracy in predicting PAH patients. Single-cell analysis showed that ARMCX3 was highly expressed in pulmonary vascular smooth muscle cells and endothelial cells. Molecular docking and drug prediction showed estradiol is a potential targeted drug for ARMCX3. 127 miRNA-TF-mRNA regulatory relationships were established. Immune cell infiltraion analysis showed that ARMCX3 is correlated with the content of immune cells.Conclusions:ARMCX3 was identified as potential biomarker of PAH based on the machine learning algorithms and bioinformatics analysis, which elucidata the molecular mechanisms underlying PAH development.

Circulation, Volume 150, Issue Suppl_1, Page A4144426-A4144426, November 12, 2024. Introduction:Intensive blood pressure (BP) control is associated with a significant reduction in the risk of heart failure (HF) or all-cause death. However, the extent to which intensive BP control-associated HF risk reduction is mediated by changes in subclinical markers of cardiovascular (CV) disease (CVD) and stage B HF is not well-characterized.Methods:Participants of the Systolic Blood Pressure Intervention Trial (SPRINT) with hypertension and available data on subclinical CVD markers at baseline and follow-up (1- or 2-year visit) were included. The key subclinical markers of CVD analyzed included chronic myocardial injury (assessed by high-sensitivity cardiac troponin I [hs-cTnI]), neurohormonal stress (assessed by N-terminal pro-B-type natriuretic peptide [NT-proBNP]), left ventricular (LV) mass (assessed by electrocardiogram Cornell voltage [CV]), and arterial stiffness (assessed by estimated pulse wave velocity [ePWV]). A counterfactual framework was used to assess the effects of the exposure and mediator on key outcomes, including 1) HF / all-cause death; 2) atherosclerotic CVD (ASCVD), including nonfatal myocardial infarction, nonfatal stroke, or CV death.Results:The present study included 8,872 participants (35% women, 31% Black). Over the 3.3-year median follow-up, there were 333 (3.8%) HF / all-cause death events and 200 (2.3%) ASCVD events. Reductions in neurohormonal stress and LV mass mediated up to 15% of the reduction in risk of HF / all-cause death with intensive BP control (Table). In contrast, treatment-related changes in chronic myocardial injury and arterial stiffness did not mediate the benefits of intensive BP reduction on HF / all-cause death risk. Furthermore, changes in any subclinical CVD markers did not mediate the effect of intensive BP control on ASCVD risk (Table).Conclusions:In this post-hoc analysis of SPRINT, improvements in neurohormonal stress and LV mass, as identified by surrogate markers of hs-cTnI and CV, were important mediators of the beneficial effects of intensive BP control in reducing the risk of HF / all-cause death. Mediators of the effect of intensive vs. standard BP control for reducing HF / all-cause death differ from those for ASCVD.

Circulation, Volume 150, Issue Suppl_1, Page ASa501-ASa501, November 12, 2024. Aims:This study evaluated the association between blood-brain barrier (BBB) disruption and the molecular weights of biomarkers in predicting neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors who received targeted temperature management (TTM) and lumbar drainage therapy.Methods:This observational study used data from a prospectively collected TTM registry at a tertiary academic hospital.Serum levels of neuron-specific enolase (NSE, 47 kDa) and S100 calcium-binding protein B (S100B, 21 kDa) were measured immediately, 24 h, 48 h, and 72 h after return of spontaneous circulation (ROSC). To assess the extent of BBB disruption, the albumin quotient (QA) was calculated at each time point of serum biomarker measurement using the formula: QA= albumin [cerebrospinal fluid] / albumin [serum]. Degrees of BBB disruption were categorized as follows: a QAvalue less than 0.007 was considered normal; a value within 0.007–0.01 indicated mild disruption; a value within 0.01–0.02 indicated moderate disruption; and a value greater than 0.02 indicated severe disruption. Prognostic performances were evaluated using the areas under receiver operating characteristic curves (AUC). The primary outcome was poor neurological outcome 6 months after ROSC defined as Cerebral Performance Category scores of 3–5.Results:A total of 562 serum biomarker levels (371 NSE and 191 S100B) in 106 patients (59% poor neurological outcome) were evaluated. Serum levels of NSE and S100B showed no statistically significant difference in prognostic performance for poor neurological outcomes (AUC 0.85 [0.81–0.88] vs. 0.83 [0.80–0.87], P=0.43). Serum NSE levels showed differences in prognostic performance depending on BBB integrity (AUC 0.65 [intact BBB] vs AUC 0.87 [disrupted BBB]), compared with S100B (AUC 0.83 [intact BBB] vs. 0.79 [disrupted BBB]) (Figure 1). In particular, serum NSE levels had higher predictive performance when the BBB was moderately or severe disrupted compared to when it was intact (Figure 2). Additionally, serum NSE levels demonstrated better predictive performance when BBB is disrupted (P< 0.001), whereas serum S100B levels demonstrated better predictive performance when BBB is intact (P = 0.004) (Figure 3).Conclusions:In this cohort study, the relationship between molecular weights of biomarkers and BBB intact/disruption demonstrated good prognostic performance for OHCA survivors. Prospective multicenter studies are needed to generalize our findings.

Circulation, Volume 150, Issue Suppl_1, Page A4140895-A4140895, November 12, 2024. Background:Red cell distribution width (RDW) is a measurement of variability in erythrocyte size and volume, routinely reported as part of a complete blood count. Recently, it has gained popularity as a novel prognostic biomarker for cardiovascular disease outcomes. Our study investigates the predictive value of pre-procedural RDW for all-cause mortality (ACM) within one year for patients undergoing transcatheter aortic valve implantation (TAVI).Methods:We comprehensively reviewed databases like PubMed, Google Scholar, Embase, and Scopus until May 2024, looking for studies reporting an association between pre-procedural RDW and outcomes in TAVI. A binary random effects model was used to calculate the pooled adjusted odds ratio (aOR), and subgroup analysis was performed. I2 statistics were used to determine the heterogeneity of studies, further enhancing the robustness of our research.Results:Our systematic review and meta-analysis included five studies (three retrospective, two prospective) encompassing 2,565 patients with a mean age of 81.32 years. Our study showed a slight female predominance (52%). The mean follow-up period was one year. Comorbidities like coronary artery disease, diabetes melitus, atrial fibrillation, prior myocardial infarction were commonly reported among the study population. Higher pre-procedural RDW was associated with increased odds of ACM at the end of one year with an unadjusted pooled OR 1.86 (95% CI: 1.30-2.67, p

Circulation, Volume 150, Issue Suppl_1, Page A4146705-A4146705, November 12, 2024. Introduction:Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is the leading cause of cardiovascular death. The pathophysiology of PE is complex and multifactorial. This study was designed to understand the relationship of thrombo-inflammatory biomarkers including endothelial dysregulation, platelet and coagulation activation, fibrinolysis, and inflammation along with blood cellular indices for 30-day mortality outcome in PE patients.Materials and Method:Citrated blood samples from 500 patients with the confirmed diagnosis of PE were collected from Loyola University Medical Center. Biomarkers including vWF, E-Selectin, P-Selectin, FVII, FIX, FX, FXIIIa, D-Dimer, PAI-1a, tPA, TAFIa, CRP, IL-6 and TNF-α were analyzed by Sandwich ELISA method. Blood cellular indices as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune-inflammation index (SII; NLR* platelets) were calculated from complete blood count. Thirty-day mortality data was obtained from chart review. Receiver operating curve (ROC) analysis to determine the optimal cutoff values, while for degree of association univariate chi-square and multivariate logistic regression analysis were performed for 30-day morality.Results:The study cohort includes 500 patients with equivalent distribution of male (52.1%) and female (47.9%) with the median age of 64-years. In first 30-day, 48 (9.7%) of the patients died. At baseline, patients who subsequently died had higher levels of vWF, P-selectin, tPA, PAI-1a, D-dimer, CRP, IL-6, TNF-α, NLR, PLR, and SII. Following ROC and univariate analysis, all the significant markers and indices were included in the multivariate logistic regression model. Of note, vWF >140 (OR: 2.68; 95%CI: 1.04-6.92), F-X 12 (OR: 5.31; 95%CI: 1.01-28.0), TNF-α >2 (OR: 2.65; 95%CI: 1.13-6.19), and NLR >7 (OR: 4.44; 95%CI: 1.76-11.19) predicted risk of 30-day mortality in PE patients (Figure 1).Conclusion:This study suggests that patients with vWF >140, FX 12, TNF-α >2, and NLR >7 at baseline were at increased risk of death in 30-days. Study also suggests the integrated role of thrombo-inflammatory biomarkers and blood cellular indices for the risk stratification and prediction of the adverse outcomes.

Circulation, Volume 150, Issue Suppl_1, Page A4146973-A4146973, November 12, 2024. Background:After heart transplantation, endomyocardial biopsy is used to monitor for acute rejection (AR). However, endomyocardial biopsy is invasive, and its conventional histological interpretation has limitations. Extracellular vesicles (EVs) are lipid bilayer vesicles secreted by various cell types into the circulation. EVs express an array of biomolecules indicative of their parent cells and act as cargo vesicles capable of delivering nucleic acids, proteins, and organelles. Here, we investigated whether AR affects the surface markers and mitochondrial positivity of plasma EVs and explored their potential for detecting AR in cardiac transplant recipients.Methods:Plasma samples were collected from participants from the Genomic Research Alliance for Transplantation (GRAfT, sponsored by NIH). Histopathology data were collected to define AR. Patients with non-rejection (NR, N=6), acute cellular rejection (ACR, N=7), antibody-mediated rejection (AMR, N=5), and a combination of ACR and AMR (ACR/AMR, N=2) were employed. Plasma EVs were isolated from a total of 71 plasma samples using a size exclusion column (qEV, IZON Science). The size distribution and concentration of the plasma EVs were evaluated by nanoparticle tracking analysis. The positivity for surface markers was assessed by flow cytometry, including CD235a (erythrocytes), CD144 (endothelial cells), CD45 (leukocytes), CD3 (T cells), CD20 (B cells), CD14 (monocytes), and CD172a (cardiomyocytes). Additionally, the positivity for mitochondrial membrane potentials in each EV cluster was measured.Results:The concentrations and mean diameter of the plasma EVs were comparable among NR, AMR, and ACR groups (2.75 x 1010/mL, 9.61 x 109/mL, and 2.70 x 1010/mL, and 192 nm and 211 nm, and 192 nm, respectively). The proportions of CD45 and CD172a-positive EVs were significantly increased in ACR/AMR compared to ACR or AMR alone. Additionally, mitochondrial markers within CD14-positive EVs exhibited a significant decrease in AMR. No significant trends were observed in the longitudinal EV profiles in each individual. Quantitative PCR confirmed that the expressions of mitochondrial DNA were decreased in the plasma EVs from AMR.Conclusion:CD172a, CD45, and mitochondrial positivity in CD14-positive EVs could serve as potential biomarkers for diagnosing AR in patients undergoing cardiac transplantation. These findings may offer insights into the pathogenesis of AMR.

Circulation, Volume 150, Issue Suppl_1, Page A4120196-A4120196, November 12, 2024. Background:Presenting symptoms risk stratify patients presenting to the Emergency Department (ED) to determine their likelihood of having a myocardial infarction (MI) and need for cardiac biomarker testing. Since the 2014 AHA/ACC non-ST segment elevation MI (NSTEMI) guideline, little is known regarding cardiac biomarker testing trends in the United States.Methods:We analyzed data from the National Hospital Ambulatory Medical Care Survey for consecutive adult ED visits between 2014 and 2021 in the United States. The primary outcome was the proportion of ED visits where cardiac biomarker testing occurred. Subgroup analysis was performed for visits with chest pain, non-chest pain anginal equivalents, and non-anginal symptoms. Survey-weighted multivariable logistic regression was used to generate adjusted odds ratios (aOR) to assess predictors of cardiac biomarker utilization.Results:In total, 87,965 ED visits were sampled, representing a weighted total of 644,531,395 visits. Cardiac biomarker testing occurred in 7.21% of all ED visits (95% CI, 6.27%-8.29%) and increased over time (Figure,P=0.03 for trend). When stratified by symptoms, utilization of testing mainly increased among patients with non-chest pain anginal equivalents (Figure,P=0.02 for trend). Cardiac biomarker testing was most frequently used for patients with chest pain (34.9%) and non-chest pain anginal equivalents (39.3%). Nonetheless, 25.8% of patients who underwent testing had no chest pain or anginal equivalents. Cardiac biomarker testing was more frequent among patients with older age (aOR 1.03 per year, 95% CI 1.03-1.04), tachycardia (aOR 1.26, 95% CI 1.13-1.41), tachypnea (aOR 1.71, 95% CI 1.47-1.98), history of heart failure (aOR 1.33, 95% CI 1.15-1.54), prior venous thromboembolism (aOR 1.43, 95% CI 1.12-1.83), and those treated in a rural setting (aOR 1.63, 95% CI 1.14-2.32).Conclusion:Cardiac biomarker testing in the ED has increased over time, mostly attributed to increased utilization among patients with a low pre-test probability of MI. Notably, 25% of individuals who underwent cardiac biomarker testing had no chest pain or anginal-equivalent symptoms. More judicious utilization of cardiac biomarker testing may be needed.

Circulation, Volume 150, Issue Suppl_1, Page ASu1001-ASu1001, November 12, 2024. Background:Progressive post-cardiac arrest syndrome (PCAS) ensues within seconds of an out-of-hospital cardiac arrest (OHCA) and results in damage over days, yet longitudinal changes in blood biomarkers during PCAS are poorly understood. We characterize novel biomarkers at early time points after return of spontaneous circulation (ROSC) and determine associations with survival.Methods:Blood plasma samples from OHCA patients were collected at 1, 6, 24, 48, 72 hours and 7 days after ROSC. Samples were analyzed using a Meso Scale Diagnostics 40-plex assay which included proinflammatory, cytokine, chemokine, angiogenesis, and vascular injury panels. The data distribution was heavily skewed, requiring log-transformation. Biomarkers were compared between survivors and non-survivors at each follow-up time point using a two-sample t-test. Mixed-effect and Generalized Estimation Equation models were used to examine the association between biomarkers and survival and assess trends over time.Results:Thirty-three patients were included, of which 54% (N=18) were males, the mean age was 57 (+/-15) years, and 54% (N=18) survived to discharge. Six out of the 40 biomarkers had a statistically significant difference in biomarker levels between survivors and non-survivors at one or more time points. At the 1-hour, macrophage derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC) were significantly higher in survivors. At 6-hour, interleukin-13 (IL-13) was the only pro-inflammatory biomarker that was significantly higher in non-survivors. At 24-hour, pro-inflammatory biomarkers interleukin-12p70 (IL-12p70) and IL-13 were higher in non-survivors, whereas vascular endothelial growth factor A (VEGF-A) was significantly higher in survivors. At 48-hours, VEGF-A was also significantly higher in survivors. At 72 hours, interleukin-8 was the only biomarker with significantly higher levels in non-survivors. Overall, IL-12p70, IL-13, and MDC levels decreased over time (p=0.02, p=0.003, p=0.01, respectively) for both survivors and non-survivors. Survivors had a lower average level for IL-12p70 (p=0.03) and for IL-13 (p=0.04), but higher average level for MDC (p=0.01) than non-survivors at discharge.Conclusion:This pilot investigation extends prior biomarker work by highlighting new biomarkers, their longitudinal changes during PCAS, and their relation to survival. Future analysis will explore differences in biomarkers for neurological outcomes after OHCA.

Circulation, Volume 150, Issue Suppl_1, Page A4137726-A4137726, November 12, 2024. Background:Mitral valve prolapse (MVP) has a prevalence of 2–3% and is a risk factor for heart failure and sudden death, but MVP diagnosis by transthoracic echocardiography (TTE) requires time and clinical expertise. We trained a deep learning model to classify MVP from TTE videos.Methods:DROID-MVP is a convolutional neural network trained to classify MVP using echocardiographer labels using 973,531 digital videos (parasternal long axis and apical views) from 45,657 studies performed in 15,728 cardiology patients at Massachusetts General Hospital. We validated DROID-MVP in 1,726 cardiology patients (4,869 studies) and 8,903 primary care patients (8,903 studies), and tested associations between predicted MVP score (range 0-1) and mitral regurgitation (MR) severity and left atrial (LA) anterior-posterior diameter in primary care patients with available measurements.Results:Of 15,728 patients (6,029 [38%] women; mean age at first TTE 61 ± 17 years) in the training set, 729 (4.6%) had at least 1 study with MVP. DROID-MVP identified MVP in both the cardiology (area under the receiver operating characteristic curve [AUC] 0.955 [95% confidence interval: 0.939-0.970]; average precision [AP] 0.716 [0.649-0.776]; prevalence 0.035) and primary care (AUC 0.966 [0.955-0.978]; AP 0.668 [0.601-0.730]; prevalence 0.022) test sets (Figure 1). Discrimination persisted across strata of MR severity (AUC range 0.877-0.987). High ( >0.67) vs low (

Circulation, Volume 150, Issue Suppl_1, Page A4136627-A4136627, November 12, 2024. Introduction:Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery lesions (CALs). Treatment with a high dose of intravenous immunoglobulin (IVIG) is the most effective therapy for the acute phase of KD. However, some very severe cases need several additional treatments and are at risk for CALs. Several scoring systems that have tried to predict IVIG-resistant patients failed in multiethnic populations.Aims:To develop the most effective biomarker for predicting refractory cases and determine the cut-off value for the development of the diagnostic kit.Methods:Multicenter, prospective, observational study was conducted at 49 hospitals in Japan between September 2017 and December 2023. The subjects consisted of 1310 KD patients, including Group 1 (n=50); treatment-resistant cases that required additional treatment of 3rd line or more (defined as refractory cases), and Group 2 (n=1260); cases that completed the treatment with 1st or 2nd line. Tenascin C (TN-C), Pentraxin 3 (PTX3), and Procalcitonin (PCT) values, which were selected by systematic review and a pilot study, were measured before initial treatment in each group. The cut-off value of the biomarker, which had the highest area under the curve (AUC), was determined.Results:All three biomarker values were significantly higher in Group 1 than Group 2 (p