Risk Stratification Of Patients Research Articles

Programmed ventricular stimulation for risk stratification in hypertrophic cardiomyopathy patients.

Programmed ventricular stimulation for risk stratification in hypertrophic cardiomyopathy patients.

Pharmacogenomics of coronary artery response to intravenous gamma globulin in kawasaki disease

Kawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that can result in acute vasculitis. The mechanism of coronary artery aneurysms (CAA) in KD despite intravenous gamma globulin (IVIG) treatment is not known. We performed a Whole Genome Sequencing (WGS) association analysis in a racially diverse cohort of KD patients treated with IVIG, both using AHA guidelines. We defined coronary aneurysm (CAA) (N = 234) as coronary z ≥ 2.5 and large coronary aneurysm (CAA/L) (N = 92) as z ≥ 5.0. We conducted logistic regression models to examine the association of genetic variants with CAA/L during acute KD and with persistence >6 weeks using an additive model between cases and 238 controls with no CAA. We adjusted for age, gender and three principal components of genetic ancestry. The top significant variants associated with CAA/L were in the intergenic regions (rs62154092 p < 6.32E–08 most significant). Variants in SMAT4, LOC100127, PTPRD, TCAF2 and KLRC2 were the most significant non-intergenic SNPs. Functional mapping and annotation (FUMA) analysis identified 12 genomic risk loci with eQTL or chromatin interactions mapped to 48 genes. Of these NDUFA5 has been implicated in KD CAA and MICU and ZMAT4 has potential functional implications. Genetic risk score using these 12 genomic risk loci yielded an area under the receiver operating characteristic curve (AUC) of 0.86. This pharmacogenomics study provides insights into the pathogenesis of CAA/L in IVIG-treated KD and shows that genomics can help define the cause of CAA/L to guide management and improve risk stratification of KD patients.

The Value of Ischemic Cardiac Biomarkers to Predict Spontaneous Breathing Trial or Extubation Failure: A Systematic Review.

Background: It is unclear whether other cardiac biomarkers than NT-proBNP can be useful in the risk stratification of patients weaning from mechanical ventilation. The aim of this study is to summarize the role of ischemic cardiac biomarkers in predicting spontaneous breathing trial (SBT) or extubation failure. Methods: We systematically searched Embase, MEDLINE, Web of Science, and Cochrane Central for studies published before January 2024 that reported the association between ischemic cardiac biomarkers and SBT or extubation failure. Data were extracted using a standardized form and methodological assessment was performed using the QUIPS tool. Results: Seven observational studies investigating four ischemic cardiac biomarkers (Troponin-T, Troponin-I, CK-MB, Myoglobin) were included. One study reported a higher peak Troponin-I in patients with extubation failure compared to extubation success (50 ng/L [IQR, 20-215] versus 30 ng/L [IQR, 10-86], p = 0.01). A second study found that Troponin-I measured before the SBT was higher in patients with SBT failure in comparison to patients with SBT success (100 ± 80 ng/L versus 70 ± 130 ng/L, p = 0.03). A third study reported a higher CK-MB measured at the end of the SBT in patients with weaning failure (SBT or extubation failure) in comparison to weaning success (8.77 ± 20.5 ng/mL versus 1.52 ± 1.42 ng/mL, p = 0.047). Troponin-T and Myoglobin as well as Troponin-I and CK-MB measured at other time points were not found to be related to SBT or extubation failure. However, most studies were underpowered and with high risk of bias. Conclusions: The association with SBT or extubation failure is limited for Troponin-I and CK-MB and appears absent for Troponin-T and Myoglobin, but available studies are hampered by significant methodological drawbacks. To more definitively determine the role of ischemic cardiac biomarkers, future studies should prioritize larger sample sizes, including patients at risk of cardiac disease, using stringent SBTs and structured timing of laboratory measurements before and after SBT.

Heartbeat Chronicles: Decoding the Interplay of Echocardiography and Heart Rate Variability in Chronic Heart Failure Patients – Unraveling the Mysteries with Traditional and Advanced 24-Hour Holter ECG Parameters

Abstract Objective Chronic heart failure (CHF) is a clinical syndrome that encompasses individuals who either have received a definitive diagnosis of heart failure or display a gradual escalation of symptoms as time elapses. Echocardiography, particularly evaluating left ventricular function, is crucial for diagnosis and prognosis. However, 24-hour Holter monitoring, focusing on heart rate variability (HRV), provides insights into autonomic dynamics and vulnerability. Recent HRV parameters offer nuanced information, enhancing risk stratification and guiding personalized interventions in CHF. The interplay between echocardiography and HRV enables a comprehensive approach, refining the management of CHF by considering both cardiac structure and autonomic regulation. Methods This prospective study at “St. Spiridon” County Hospital involved 80 patients with left ventricular ejection fraction (LVEF) &lt; 50%. The diagnosis was according to standard clinical echocardiography, laboratory panel, and Holter ECG monitoring. Results Unexpectedly, no statistically significant relationship was found between commonly used HRV parameters and echocardiographic parameters. Further analyses showed statistically significant associations between non-traditional HRV parameters and E/A ratio, E/E’, and S’ lateral and septal. Additionally, modifications in HRV parameters were correlated with mitral valve deceleration time, left atrial volume index, estimated pulmonary artery systolic pressure, and cardiac output. Conclusions Less commonly used Holter ECG parameters, such as acceleration capacity, deceleration capacity, and triangular index, demonstrated significant diagnostic efficacy, especially when conventional HRV parameters were normal. This highlights the importance of incorporating non-traditional HRV parameters in CHF patient risk stratification, urging further exploration through comprehensive multicenter studies for long-term prognostic implications.

Predictive models and applicability of artificial intelligence-based approaches in drug allergy.

Drug allergy is responsible for a huge burden on public healthcare systems, representing in some instances a threat for patient's life. Diagnosis is complex due to the heterogeneity of clinical phenotypes and mechanisms involved, the limitations of in vitro tests, and the associated risk to in vivo tests. Predictive models, including those using recent advances in artificial intelligence, may circumvent these drawbacks, leading to an appropriate classification of patients and improving their management in clinical settings. Scores and predictive models to assess drug allergy development, including patient risk stratification, are scarce and usually apply logistic regression analysis. Over recent years, different methods encompassed under the general umbrella of artificial intelligence, including machine and deep learning, and artificial neural networks, are emerging as powerful tools to provide reliable and optimal models for clinical diagnosis, prediction, and precision medicine in different types of drug allergy. This review provides general concepts and current evidence supporting the potential utility of predictive models and artificial intelligence branches in drug allergy diagnosis.

Impact of Risk Stratification in Patients With Diabetes Mellitus in a Health System Specialty Pharmacy Setting

Background: Integrated pharmacist care into health systems results in significant A1c reduction and improved outcomes in patients with diabetes. However, little is known about the adoption of Health System Specialty Pharmacy (HSSP) chronic disease management (CDM) services within diabetes clinics. Risk stratification is proven to enhance care in various patient populations. Objective: The objective of this study is to describe how the implementation of risk stratification in the HSSP setting results in optimized patient outcomes in diabetes. Method: This is a retrospective descriptive study reporting the results of expanding the HSSP care model to implement risk stratified CDM services for patients with diabetes. A total of 285 patients were enrolled in the HSSP CDM pharmacy services and were stratified into high- or low-risk groups. Results: Eighty-eight patients were stratified as high-risk with an average baseline A1c of 11.47% and a most recent average of 8.84%. The remaining 285 patients were stratified into the low-risk group. Their average baseline A1c was 7.48% and the last recorded average A1c was 7.15%. Patients not enrolled in HSSP CDM services (N = 100) had a lower reduction in average A1c compared to patients enrolled in the program. Conclusion: Patients stratified into high- and low-risk groups had greater reductions in A1c compared to patients who did not use HSSP CDM services. These results showcase the success of risk stratification and demonstrate the impact HSSP has on patients needing CDM services and outlines a strategy to provide the greatest impact in a high-volume patient population.

Prognostic Significance of Double-Expresser Status in Diffuse Large B-cell lymphoma: Experience from a Tertiary Care Cancer Centre in India

Background: Diffuse large B-cell lymphoma (DLBCL) is a neoplasm of medium or large B lymphoid cells with a diffuse histopathologic growth pattern. Co-expression of MYC and BCL2 proteins in DLBCL by immunohistochemistry (IHC) is referred to as the double-expresser (DE) phenotype and is associated with inferior survival. Objectives of this study were to assess the DE status in DLBCL and to assess its utility in predicting the prognosis in DLBCL. Methods: This was a retrospective study conducted in a tertiary care cancer centre. Study population included all the cases of DLBCL, NOS diagnosed in the centre in 2012. MYC and BCL2 protein expression were analysed by immunohistochemistry. The prognostic significance of double-expressers was analysed by comparing progression free survival (PFS) and overall survival (OS) of double-expressers and non-double expressers using appropriate statistical methods. All the data were analysed using SPSS 11 software. Kaplan-Meier method was used to estimate the survival probability. A significant difference in survival between various prognostic factors was tested using the log-rank test. Prognostic factors were assessed using univariate and multivariate Cox-regression model. A P- value &lt; 0.05 was considered to be statistically significant. Results: Double-Expresser lymphoma (DEL) constituted 22.2% (n=18) of all cases of DLBCL, NOS. DE status was associated with shorter PFS (P-value = 0.049) and OS (P-value = 0.015). Conclusion: DE status is associated with poor prognosis in DLBCL, NOS. Assessment of MYC and BCL2 by IHC represents a rapid and inexpensive approach to risk-stratify patients with DLBCL at the time of diagnosis.

Clinical implications of haemodynamics in symptomatic intracranial atherosclerotic stenosis by computational fluid dynamics modelling: a systematic review

BackgroundRecently, computational fluid dynamics (CFD) has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis (sICAS) and investigate the clinical implications of its haemodynamic features, which were systematically...

Evaluating longitudinal cytomegalovirus-specific humoral immune responses and association with DNAemia risk in seropositive lung transplant recipients

BackgroundCytomegalovirus (CMV) is the most common viral infection among lung transplant recipients and is associated with chronic lung allograft dysfunction. There is a need for better therapeutics as well as biomarkers to enable effective stratification of CMV seropositive patient risk for developing CMV DNAemia to inform prophylaxis duration. MethodsCMV-specific IgG binding and functional responses were evaluated in a discovery cohort of longitudinal plasma samples from 51 CMV seropositive human lung transplant recipients, collected as part of the CTOT-20 and CTOT-22 consortium studies. Pre-transplant plasma from an additional 43 CMV seropositive lung transplant recipients were evaluated as a validation cohort. ResultsIn the discovery cohort with longitudinal samples, pre-transplant plasma IgG binding to CMV surface glycoproteins gH/gL, gH/gL/gO, and pentameric complex (PC), as well as neutralization of CMV in epithelial cells are associated with increased risk of CMV DNAemia post-prophylaxis. However, these results were not confirmed by the validation cohort. ConclusionWhile quantification of pre-transplant CMV-specific antibody responses showed association with DNAemia in the discovery cohort, additional clinical variables and/or known risk factors for CMV, such as patient CMV-specific T-cell responses, may need to be considered in combination with humoral immunity to effectively stratify risk of CMV DNAemia.

Telephone triage of chest pain in out-of-hours primary care: external validation of a symptom-based prediction rule to rule out acute coronary syndromes.

Telephone triage is pivotal for evaluating the urgency of patient care, and in the Netherlands, the Netherlands Triage Standard (NTS) demonstrates moderate discrimination for chest pain. To address this, the Safety First Prediction Rule (SFPR) was developed to improve the safety of ruling out acute coronary syndrome (ACS) during telephone triage. We conducted an external validation of the SFPR using data from the TRACE study, a retrospective cohort study in out-of-hours primary care. We evaluated the diagnostic accuracy assessment for ACS, major adverse cardiovascular events (MACE), and major events within 6 weeks. Moreover, we compared its performance with that of the NTS algorithm. Among 1404 included patients (57.3% female, 6.8% ACS, 8.6% MACE), the SFPR demonstrated good discrimination for ACS (C-statistic: 0.79; 95%-CI: 0.75-0.83) and MACE (C-statistic: 0.79; 95%-CI: 0.0.76-0.82). Calibration was satisfactory, with overestimation observed in high-risk patients for ACS. The SFPR (risk threshold 2.5%) trended toward higher sensitivity (95.8% vs. 86.3%) and negative predictive value (99.3% vs. 97.6%) with a lower negative likelihood ratio (0.10 vs. 0.34) than the NTS algorithm. The SFPR proved robust for risk stratification in patients with acute chest pain seeking out-of-hours primary care in the Netherlands. Further prospective validation and implementation are warranted to refine and establish the rule's clinical utility.

Elevated Serum Alkaline Phosphatase is an Independent Predictor of Complications After Lumbar Spinal Fusion

BackgroundAlkaline phosphatase (ALP) is an enzyme which has been proven useful as a biomarker for bone turnover and inflammation. We hypothesized that high serum ALP levels are associated with increased complication rates following lumbar spinal fusion. MethodsLumbar spinal fusion procedures from 2005-2019 were queried from the national Surgical Quality Improvement Program (NSQIP) database. Serum alkaline phosphatase levels were stratified into low <44 IU/L, normal 44-147 IU/L, and high >147 IU/L. A risk-adjusted multivariate logistic regression was used to analyze ALP as an independent risk factor for complications. ResultsA total of 16,441 patients who underwent lumbar fusion procedures were included. Adjusted multivariate logistic regression analysis demonstrated that patients with a high serum ALP level had a significantly increased risk for developing septic shock (OR 4.68, 95% CI 1.83-11.97), pneumonia (OR 2.89, 95% CI 1.59-5.25), requiring a transfusion (OR 2.09, 95% CI 1.68-2.59), reoperation within 30 days (OR 1.68, 95% CI 1.12-2.52), readmission within 30 days (OR 1.60, 95% CI 1.16-2.21), increased length of stay (OR 1.87, 95% CI 1.49-2.36), and nonhome discharge (OR 2.18, 95% CI 1.80-2.66). Clinical RelevanceSerum alkaline phosphatase is a valuable and readily available tool for preoperative risk stratification of patients undergoing lumbar spinal fusion. ConclusionsElevated serum ALP in patients undergoing lumbar fusion procedures is associated with increased risk for multiple in-hospital complications as well as higher rates of readmission and reoperation.

Residual Coronary Risk Factors Associated With Long-Term Clinical Outcomes in Patients With Coronary Artery Disease Treated With High- vs. Low-Dose Statin Therapy - REAL-CAD Substudy.

It remains unclear which comorbidities, other than lipid parameters, or combination of comorbidities, best predicts cardiovascular events in patients with known coronary artery disease (CAD) treated with statins. Therefore, we aimed to identify the nonlipid-related prognostic factors and risk stratification of patients with stable CAD enrolled in the REAL-CAD study. Blood pressure, glucose level, and renal function were considered as risk factors in the 11,141 enrolled patients. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unstable angina. The secondary composite endpoint was the primary endpoint and/or coronary revascularization. A significantly worse prognosis at the primary endpoint was observed in the estimated glomerular filtration rate (eGFR) ≤60 group, and the combination of eGFR ≤60 and HbA1c ≥6.0 was the worst (hazard ratio (HR) 1.66; P<0.001). However, even in the eGFR >60 group, systolic blood pressure (SBP) ≥140 mmHg met the secondary endpoint (HR 1.33; P=0.006), and the combination of eGFR ≤60 and HbA1c ≥6.0 was also the worst at the secondary endpoint (HR 1.35; P=0.002). Regarding nonlipid prognostic factors contributing to the incidence of cardiovascular events in statin-treated CAD patients, renal dysfunction was the most significant, followed by poor glucose control and high SBP.

Use of cardiac MRI and wearable defibrillator to identify patients at low risk for arrhythmic events: single center experience

Abstract Introduction In our Center, patients (pts) with newly diagnosed HF and reduced LVEF underwent MRI to determine the presence and extension of delayed enhancement (DE) or scar areas. These patients were discharged with a wearable cardioverter defibrillator (WCD) as monitoring and temporary antiarrhythmic therapy until a three-month follow-up (FU). Subsequent FU was performed at 6 and 12 months. Methods From May 2016 to July 2023, 120 consecutive pts (97 M; mean age 65.3y±9.7y) with reduced EF (28.5%±8.5%) on OMT, were discharged with WCD and included in clinical FU. Coronary anatomy was acquired in 119 pts: absence of coronary atherosclerosis (ats) (44 pts); not significant ats(39 pts); Significant ats(36 pts). 1 pt did not perform angiography due to thyrotoxicosis. MRI was performed in 95 pts (EDV 181.9 ± 48.7 ml/m2; Mass 96.9± 23.4 g/m2, LVEF MRI 26.8% ±9.2). FU was performed at 3 months in all patients; at 6 months in 111pts and at 12 months in 107pts. WCD is still present in 4 pts. LGE score was used to quantify myocardial fibrosis by defining reduced extension as LGE score &amp;lt;5. Results MRI identified 57 pts with a delayed enhancement(DE) midwall pattern and in 13 of these there was a regional ischemic pattern also; 27 pts with regional scar; 18 pts without DE. During follow-up, 87 patients (75%) recovered LVEF function at 3 months (LVEF 44.3±6.3%) and were no longer indicated for ICD. 29 pts were implanted with ICD (25%). These patients had higher absolute and indexed volumes on MRI (p 0.053; p 0.042) and a greater presence of ischemic pattern (p 0.05). The LGE score was low in 76 pts (&amp;lt;5). A low LGE score is linked to the recovery of LVEF (p 0.04). Patients who undergo ICD had greater DE extension (p 0.01). 1 pt with a high LGE score (36.6) refused ICD and underwent SCD at 6 months. In pts with LGE score &amp;lt;5, 1 major arrhythmic event occurred (1 SVT in pt with ICD). In pts with LGE score &amp;gt;5, 3 major events occurred (1 shock on VF, 1 ATP on SVT, 1 SCD). 1 pt with extensive anterior akinesia who refused MRI presented 1 shock on VF at 6 months. 1 pt with partial recovery of LVEF and extensive anterior akinesia refused MRI and presented cardiac arrest for VF at 6 months. Conclusions MRI has become essential for risk stratification in patients with reduced LVEF. It is useful for identifying pts with severe impairment LVEF and low risk of events. The absence of DE and/or the presence of a low LGE score are linked to a low risk of arrhythmic events at 6 and 12 months and to a higher probability of recovery LVEF regardless of the etiology. The volumetric dimensions found on MRI are inversely linked to the recovery of LVEF. The WCD represents additional safety with excellent compliance in pts who still do not have clear indications for a definitive ICD. The combined MRI and WCD strategy can help to reduce the need for definitive ICD and therefore healthcare costs. The size of the sample does not allow definitive conclusions.

Predicting Risks of Dry Eye Disease Development Using a Genome-Wide Polygenic Risk Score Model.

The purpose of this study was to conduct a large-scale genome-wide association study (GWAS) and construct a polygenic risk score (PRS) for risk stratification in patients with dry eye disease (DED) using the Taiwan Biobank (TWB) databases. This retrospective case-control study involved 40,112 subjects of Han Chinese ancestry, sourced from the publicly available TWB. Cases were patients with DED (n = 14,185), and controls were individuals without DED (n = 25,927). The patients with DED were further divided into 8072 young (<60 years old) and 6113 old participants (≥60 years old). Using PLINK (version 1.9) software, quality control was carried out, followed by logistic regression analysis with adjustments for sex, age, body mass index, depression, and manic episodes as covariates. We also built PRS prediction models using the standard clumping and thresholding method and evaluated their performance (area under the curve [AUC]) through five-fold cross-validation. Eleven independent risk loci were identified for these patients with DED at the genome-wide significance levels, including DNAJB6, MAML3, LINC02267, DCHS1, SIRPB3P, HULC, MUC16, GAS2L3, and ZFPM2. Among these, MUC16 encodes mucin family protein. The PRS model incorporated 932 and 740 genetic loci for young and old populations, respectively. A higher PRS score indicated a greater DED risk, with the top 5% of PRS individuals having a 10-fold higher risk. After integrating these covariates into the PRS model, the area under the receiver operating curve (AUROC) increased from 0.509 and 0.537 to 0.600 and 0.648 for young and old populations, respectively, demonstrating the genetic-environmental interaction. Our study prompts potential candidates for the mechanism of DED and paves the way for more personalized medication in the future. Our study identified genes related to DED and constructed a PRS model to improve DED prediction.

Impact of Relative Improvement in Quantitative Flow Ratio on Clinical Outcomes After Percutaneous Coronary Intervention - A Subanalysis of the PANDA III Trial.

The clinical impact of relative improvements in coronary physiology in patients receiving percutaneous coronary intervention (PCI) for coronary artery disease (CAD) remains undetermined.Methods and Results: The quantitative flow ratio (QFR) recovery ratio (QRR) was calculated in 1,424 vessels in the PANDA III trial as (post-PCI QFR-pre-PCI QFR)/(1-pre-PCI QFR). The primary endpoint was the 2-year vessel-oriented composite endpoint (VOCE; a composite of vessel-related cardiac death, vessel-related non-procedural myocardial infarction, and ischemia-driven target vessel revascularization). Study vessels were dichotomously stratified according to the optimal QRR cut-off value. During the 2-year follow-up, 41 (2.9%) VOCEs occurred. Low (<0.86) QRR was associated with significantly higher rates of 2-year VOCEs than high (≥0.86) QRR (6.6% vs. 1.4%; adjusted hazard ratio [aHR] 5.05; 95% confidence interval [CI] 2.53-10.08; P<0.001). Notably, among vessels with satisfactory post-procedural physiological results (post-PCI QFR >0.89), low QRR also conferred an increased risk of 2-year VOCEs (3.7% vs. 1.4%; aHR 3.01; 95% CI 1.30-6.94; P=0.010). Significantly better discriminant and reclassification performance was observed after integrating risk stratification by QRR and post-PCI QFR to clinical risk factors (area under the curve 0.80 vs. 0.71 [P=0.010]; integrated discrimination improvement 0.05 [P<0.001]; net reclassification index 0.64 [P<0.001]). Relative improvement of coronary physiology assessed by QRR showed applicability in prognostication. Categorical classification of coronary physiology could provide information for risk stratification of CAD patients.

Risk Assessment in Patients with Symptomatic and Asymptomatic Preexcitation (RASAP)

Abstract Background Controversy remains as to whether exercise stress test (EST) is sufficient for risk evaluation in patients with preexcitation. Purpose This study aims to clarify the usefulness of EST in risk stratification in both asymptomatic and symptomatic patients, presenting with preexcitation. Methods This prospective study includes consecutive asymptomatic and symptomatic patients with preexcitation, referred for risk assessment. All participants performed an incremental EST (bicycle), prior to an electrophysiology study (EPS). Primary data from the EST included loss of preexcitation during exercise and from EPS included measurement of accessory pathway effective refractory period (APERP), shortest preexcited RR interval (SPERRI), and inducible arrythmia with use of a beta-adrenergic receptor agonist if deemed necessary. Results One hundred and sixty-four patients (59 asymptomatic, 105 symptomatic) completed an EST and EPS. Forty-five patients (27%) demonstrated low-risk findings on EST, of which 19 were asymptomatic and 26 were symptomatic. Six patients with low-risk EST findings had SPERRI/APERP≤250 ms at EPS, two of them were asymptomatic. The sensitivity, specificity, positive and negative predictive value (PPV, NPV) and accuracy of low-risk EST for excluding patients with SPERRI/APERP≤250 ms were 29%, 91%, 80%, 48%, and 55% respectively. The number of patients with inducible arrhythmia at EPS was similar in the asymptomatic 36 (69%) and in the symptomatic 73 (61%) group. Conclusions Sudden loss of preexcitation during EST has a low sensitivity and low NPV in excluding high-risk APs. EPS with use of isoproterenol should be considered to accurately assess the risk of patients with preexcitation regardless of symptoms.Figure

The prognostic value of Dickkopf-3 (Dkk3), TGFB1 and ECM-1 in prostate cancer

Prostate cancer (PCa) is considered one of the most common cancers worldwide. Despite advances in patient diagnosis, management, and risk stratification, 10%–20% of patients progress to castration-resistant disease. Our previous report highlighted a protective role of Dickkopf-3 (DKK3) in PCa stroma. This role was proposed to be mediated through opposing extracellular matrix protein 1 (ECM-1) and TGF-β signalling activity. However, a detailed analysis of the prognostic value of DKK3, ECM-1 and members of the TGF-β signalling pathway in PCa was not thoroughly investigated. In this study, we explored the prognostic value of DKK3, ECM-1 and TGFB1 using a bioinformatical approach through analysis of large publicly available datasets from The Cancer Genome Atlas Program (TGCA) and Pan-Cancer Atlas databases. Our results showed a significant gradual loss of DKK3 expression with PCa progression (p &amp;lt; 0.0001) associated with increased DNA methylation in its promoter region (p &amp;lt; 1.63E-12). In contrast, patients with metastatic lesions showed significantly higher levels of TGFB1 expression compared to primary tumours (p &amp;lt; 0.00001). Our results also showed a marginal association between more advanced tumour stage presented as positive lymph node involvement and low DKK3 mRNA expression (p = 0.082). However, while ECM1 showed no association with tumour stage (p = 0.773), high TGFB1 expression showed a significant association with more advanced stage presented as advanced T3 stage compared to patients with low TGFB1 mRNA expression (p &amp;lt; 0.001). Interestingly, while ECM1 showed no significant association with patient outcome, patients with high DKK3 mRNA expression showed a significant association with favourable outcomes presented as prolonged disease-specific (p = 0.0266), progression-free survival (p = 0.047) and disease-free (p = 0.05). In contrast, high TGFB1 mRNA expression showed a significant association with poor patient outcomes presented as shortened progression-free (p = 0.00032) and disease-free survival (p = 0.0433). Moreover, DKK3, TGFB1 and ECM1 have acted as immune-associated genes in the PCa tumour microenvironment. In conclusion, our findings showed a distinct prognostic value for this three-gene signature in PCa. While both DKK3 and TGFB1 showed a potential role as a clinical marker for PCa stratification, ECM1 showed no significant association with the majority of clinicopathological parameters, which reduce its clinical significance as a reliable prognostic marker.

The Use of Metabolomes in Risk Stratification of Heart Failure Patients: Protocol for a Scoping Review.

Heart failure (HF) is a significant health problem that is often associated with major morbidity and mortality. Metabolic abnormalities occur in HF and may be used to identify individuals at risk of developing the condition. Furthermore, these metabolic changes may play a role in the pathogenesis and progression of HF. Despite this knowledge, the utility of metabolic changes in diagnosis, management, prognosis, and therapy for patients with chronic HF has not been systematically reviewed. This scoping review aims to systematically appraise the literature on metabolic changes in patients with HF, describe the role of these changes in pathogenesis, progression, and care, and identify knowledge gaps to inform future research. This review will be conducted using a strategy based on previous reports, the JBI Manual for Evidence Synthesis, and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive search of electronic databases (Medline, EBSCOhost, Scopus, and Web of Science) will be conducted using keywords related to HF, myocardial failure, metabolomes, metabonomics, and analytical chemistry techniques. The search will include original peer-reviewed research papers (clinical studies conducted on humans and systematic reviews with or without a meta-analysis) published between January 2010 and September 2023. Studies that include patients with HF younger than 18 years or those not published in English will be excluded. Two authors (UGA and MB) will screen the titles and abstracts independently and perform a full-text screen of the relevant and eligible papers. Relevant data will be extracted and synthesized, and a third author or group will be consulted to resolve discrepancies. This scoping review will span from January 2010 to September 2023, and the results will be published in a peer-reviewed, open-access journal as a scoping review in 2024. The presentation of the findings will use the PRISMA-ScR flow diagram and descriptive and narrative formats, including tables and graphical displays, to provide a comprehensive overview of the extracted data. This review aims to collect and analyze the available evidence on metabolic changes in patients with HF, aiming to enhance our current understanding of this topic. Additionally, this review will identify the most commonly used and suitable sample, analytical method, and specific metabolomes to facilitate standardization, reproducibility of results, and application in the diagnosis, treatment, and risk stratification of patients with HF. Finally, it is hoped that this review's outcomes will inspire further research into the metabolomes of patients with HF in low- and middle-income countries. Open Science Framework; https://osf.io/sp6xj. DERR1-10.2196/53905.

Study of GRACE and TIMI Risk Scores’ Application in the Risk Stratification in Patients with Acute Coronary Syndrome in Qinghai

Study of GRACE and TIMI Risk Scores’ Application in the Risk Stratification in Patients with Acute Coronary Syndrome in Qinghai

#377 Assessment of kidney function by creatinine and cystatin C and cardiovascular outcomes in patients with atrial fibrillation

Abstract Background and Aims Atrial fibrillation (AF) in patients with chronic kidney disease are at an increased risk for ischemic and bleeding events and all-cause mortality. Accurate kidney function estimation is key for risk assessment. Creatinine is commonly used to calculate the Glomerular Filtration Rate (GFR). However, cystatin C has been described to be more sensitive than creatinine independent of muscle mass, autoimmune disease, inflammation or consuming diseases. Our aim was to evaluate the associations between kidney function, assessed by creatinine and cystatin C, and cardiovascular events (CVE), its individual components, and major bleedings. Method We enrolled 326 AF patients into two prospective, multicenter cohort studies. Creatinine and cystatin C were measured at baseline and clinical outcome events were assessed yearly. We calculated GFR using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula based on either creatinine (GFRcr), cystatin C (GFRcy) or both (GFRc2). Primary outcome was major CVE, defined as a composite of stroke or systemic embolism, myocardial infarction and cardiovascular death. Secondary outcomes were the individual components of major CVE and major bleeding. Multivariable adjusted Cox regression analyses were built to evaluate the associations between kidney function and outcome events. Results Mean age was 56 ± 9 years and 37% were female. Mean creatinine and cystatin С levels were 112 ± 21 μmol/l and 1.6 ± 0.3 mg/l, respectively, translating to a GFRc2 of 58.2 ± 16.8 ml/min/1.73 m2. Over a median follow-up of 2 years, the incidence rates for major CVE (per 100 person-years) across quartiles (Q1-Q4) of GFRc2 were 23.1, 20.3, 17.6 and 14.7, respectively. When using multivariable adjusted Cox regression analysis, major CVE was significantly associated with GFRcr (per 1 standard deviation: HR 0.89 (95% CI 0.79; 0.98) p = 0.01), GFRcy (HR 0.65 (CI 0.53; 0.72), p &amp;lt; 0.001) and GFRc2 (HR 0.74 (CI 0.63; 0.82), p &amp;lt; 0.001). This association was mainly driven by cardiovascular death. Major bleeding was associated with GFRcy (HR 0.78 (0.64-0.93) p = 0.001) and GFRc2 (HR 0.82 (0.69-0.97), p = 0.01), but not with GFRcr (HR 0.93 (95% CI 0.83-1.1) p = 0.33). Conclusion Among AF patients, GFR equations including cystatin C were associated both with major CVE and bleeding events, while creatinine based GFR equations were only associated with major CVE. Therefore, Cystatin C based GFR equations might offer more comprehensive risk stratification in patients with AF.