Strong Predictor Of Mortality Research Articles

Whole blood transcriptional profiles and the pathogenesis of tuberculous meningitis.

Mortality and morbidity from tuberculous meningitis (TBM) are common, primarily due to inflammatory response to Mycobacterium tuberculosis infection, yet the underlying mechanisms remain poorly understood. We aimed to uncover genes and pathways associated with TBM pathogenesis and mortality, and determine the best predictors of death, utilizing whole-blood RNA sequencing from 281 Vietnamese adults with TBM, 295 pulmonary tuberculosis (PTB), and 30 healthy controls. Through weighted gene co-expression network analysis, we identified hub genes and pathways linked to TBM severity and mortality, with a consensus analysis revealing distinct patterns between HIV-positive and HIV-negative individuals. We employed multivariate elastic-net Cox regression to select candidate predictors of death, then logistic regression and internal bootstrap validation to choose best predictors. Increased neutrophil activation and decreased T and B cell activation pathways were associated with TBM mortality. Among HIV-positive individuals, mortality associated with increased angiogenesis, while HIV-negative individuals exhibited elevated TNF signaling and impaired extracellular matrix organization. Four hub genes-MCEMP1, NELL2, ZNF354C, and CD4-were strong TBM mortality predictors. These findings indicate that TBM induces a systemic inflammatory response similar to PTB, highlighting critical genes and pathways related to death, offering insights for potential therapeutic targets alongside a novel four-gene biomarker for predicting outcomes.

Whole blood transcriptional profiles and the pathogenesis of tuberculous meningitis

Mortality and morbidity from tuberculous meningitis (TBM) are common, primarily due to inflammatory response to Mycobacterium tuberculosis infection, yet the underlying mechanisms remain poorly understood. We aimed to uncover genes and pathways associated with TBM pathogenesis and mortality, and determine the best predictors of death, utilizing whole-blood RNA sequencing from 281 Vietnamese adults with TBM, 295 pulmonary tuberculosis (PTB), and 30 healthy controls. Through weighted gene co-expression network analysis, we identified hub genes and pathways linked to TBM severity and mortality, with a consensus analysis revealing distinct patterns between HIV-positive and HIV-negative individuals. We employed multivariate elastic-net Cox regression to select candidate predictors of death, then logistic regression and internal bootstrap validation to choose best predictors. Increased neutrophil activation and decreased T and B cell activation pathways were associated with TBM mortality. Among HIV-positive individuals, mortality associated with increased angiogenesis, while HIV-negative individuals exhibited elevated TNF signaling and impaired extracellular matrix organization. Four hub genes—MCEMP1, NELL2, ZNF354C, and CD4—were strong TBM mortality predictors. These findings indicate that TBM induces a systemic inflammatory response similar to PTB, highlighting critical genes and pathways related to death, offering insights for potential therapeutic targets alongside a novel four-gene biomarker for predicting outcomes.

Significance of Initial Chest CT Severity Score (CTSS) and Patient Characteristics in Predicting Outcomes in Hospitalized COVID-19 Patients: A Single Center Study

The aim of this study is to examine the prognostic role of initial chest computed tomography severity score index (CTSS) and its association with demographic, socio-epidemiological, and clinical parameters in COVID-19 hospitalized patients. A retrospective study included patients who were hospitalized in the COVID Hospital of the Clinical Hospital Center Kosovska Mitrovica from July 2020 to March 2022. We compared patient characteristics and outcome of their hospital stay with values of CT severity score (mild, moderate, and severe form of the disease). Patients with severe disease were statistically significantly older, they treated more days, and they presented statistically significant highest mortality rate compared to mild and moderate forms. Smokers and obese were significantly more frequent among patients with higher CT, while vaccinated patients were more common among those with a mild form. Biochemical parameters at admission also showed statistical significance between the examined groups. We can conclude that by employing the initial CT severity score as the strongest predictor of mortality, it is possible to predict the outcome in hospitalized patients. A comprehensive examination of the patient upon admission, including determining the extent of inflammatory changes in the lungs using computed tomography, the levels of oxygen saturation, and other laboratory parameters, can assist doctors in making an adequate clinical evaluation and apply appropriate therapeutic protocols in the treatment of COVID-19.

Comorbidities and risk of death in atrial fibrillation: a nationwide cohort study

Abstract Background Atrial fibrillation (AF) is associated with increased mortality, cardiovascular morbidity, and risk of stroke. With aging population, the number of AF patients is increasing, and they present with more comorbidities representing a major public health challenge. Purpose The influence of concomitant diseases on survival of patients with AF is not well established. Using data from a comprehensive nationwide cohort study, we studied the influence of several comorbidities on one-year mortality after the diagnosis of new-onset AF. Methods All patients with newly diagnosed AF in Finland 2007-17 were identified from nationwide registries. Individualized data on concomitant diseases were gathered from ICD-10 diagnoses during hospitalizations and outpatient visits in primary and specialist care and from drug reimbursements registries. Patients were followed until the end of 2018 from the causes of death registry, which records every death in the country. All-cause mortality associated with several comorbidities per 1000 person-years was determined, and relative risk (RR) of death was calculated. Results A total of 229,321 patients (mean age 73 ± 13.2 years, 50.0% male) with new-onset AF were identified. Mean age of men and women with new-onset AF was 69.4 ± 13.4 and 77.1 ± 11.8 years, respectively. During the one-year follow-up, 11.6% of men and 13.7% of women died. Heart failure, kidney disease and dementia were the strongest predictors of mortality and were associated with an over threefold risk of death within one year. Cancer, history of bleeding and vascular disease carried over twofold risk of death. In addition, hypertension, diabetes, alcohol abuse and history of stroke predicted mortality. The risk of death associated with these comorbidities is presented in Table. Conclusions Several comorbidities were associated with significantly increased risk of death within one year of the AF diagnosis. Heart failure, kidney disease and dementia were strongest predictors of subsequent mortality with over threefold risk. These data will inform the treatment decisions regarding AF patients with comorbidities.

RV-PA uncoupling is a strong predictor of 3-year all-cause mortality in transthyretin amyloid cardiomyopathy

Abstract Background Right ventricle to pulmonary artery coupling (RV-PAc) describes the right ventricle's ability to adjust to an increased afterload which, in case of transthyretin amyloid cardiomyopathy (ATTR-CM), can result from increased left ventricular diastolic stiffness due to fibril deposition. While RV-PAc is a validated prognostic parameter in pulmonary arterial hypertension (PAH), its prognostic relevance in ATTR-CM remains unclear. This study sought to evaluate the prognostic implications of impaired RV-PAc on survival in ATTR-CM. Methods In this two-centre study, RV-PAc was investigated by the echocardiographic surrogate of ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP) in 418 ATTR-CM patients, all treated with TTR stabilizer. The primary outcome was all-cause mortality. Receiver operation curves and Youden’s J analysis were applied to identify an optimal cut-off value of RV-PAc ratio. Results Within a median time of 631 (IQR 361-983) days after diagnosis, 14.4% of patients died. RV-PAc ratio at first presentation emerged as a robust marker for risk stratification with a determined optimal cut-off of 0.382mm/mmHg (area under the curve (AUC) 0.746, 95% CI 0.68-0.82). Patients with RV-PAc ratio ≤0.382mm/mmHg (impaired RV-PAc, n=158) exhibited significantly lower survival (HR 4.07, 95% CI 2.26-7.33, p<0.001) within 3 years of follow up than those with RV-PAc ratio > 0.382mm/mmHg. In multivariate Cox regression analysis, incorporating a range of known prognostic variables, reduced RV-PAc was a strong echocardiographic predictor of mortality (Hazard Ratio (HR) 2.99, 95% Confidence Interval (CI) 1.63-5.51, p <0.001). Conclusion Impaired adaption of the RV to increased afterload is associated with worse outcome in ATTR-CM patients. RV-PAc ratio can serve as an echocardiographic predictor for all-cause mortality within three years after diagnosis. Therefore, determination of RV-PAc could improve risk stratification for ATTR-CM patients.Figure_1_Kaplan-Meier curves

CSTB, FABP4, IBP-1 and ST2 are strong predictors of mortality after transcatheter edge-to-edge mitral valve repair

Abstract Introduction Various clinical characteristics have emerged as prognostic factors in patients undergoing transcatheter edge-to-edge mitral valve repair (M-TEER). The use of biomarkers for outcome prediction has enormous potential. The goal of this study was to identify novel biomarkers linked with adverse events after M-TEER. Methods We prospectively included 242 patients undergoing M-TEER at our center and obtained pre-procedural blood samples for biomarker analysis. Additionally, 94 follow-up samples were taken three months after M-TEER. A commercial multiplex protein assay (Cardiovascular III, Olink, Uppsala, Sweden) was used to quantify expression levels of 92 defined biomarkers. We analyzed differences in biomarker expression levels between patients that had died within one year after M-TEER and patients that had survived. Results 39 patients (16.3%) had died within one year after M-TEER. In these patients the most significantly upregulated biomarkers were NT-proBNP (expression 3.0-fold compared to survivors, p < 0.001), Cystatin B (CSTB; 2.0-fold, p < 0.001), fatty acid binding protein 4 (FABP4; 2.0-fold, p < 0.001), insulin-like growth factor-binding protein 1 (IBP-1; 1.9-fold, p < 0.001) and suppression of tumourigenicity 2 (ST2; 1.7-fold, p < 0.001). In non-survivors, expression levels of NT-proBNP (6.1-fold, p = 0.036), CSTB (3.2-fold, p = 0.050), FABP4 (3.7-fold, p = 0.037) and ST2 (2.1-fold, p = 0.017) were persistently elevated at the time of follow-up. Since its prognostic impact has already been described elsewhere, NT-proBNP was excluded from further analysis. Kaplan Meier analysis for 1-year mortality was carried out using tertiles of the respective biomarker expression levels. Mortality risk increased significantly with rising expression levels (CSTB: 3.4% in tertile 1, 12.2% in tertile 2, 37.9% in tertile 3; FABP4: 5.1%, 14.2% and 31.7%; IBP-1: 3.3%, 13.2% and 36.2%; ST2: 4.9%, 11.9% and 36.7%; p by log-rank-test < 0.001 for all biomarkers). Patients in which all 4 biomarkers were elevated to the highest tertile had an excessively high mortality risk of 52.9 vs. 13.5% (p by log-rank-test < 0.001). Receiver operating characteristic (ROC) analysis suggested higher predictive performances for mortality of all 4 biomarkers as compared to the EuroSCORE II (CSTB: area under the curve (AUC) 78.1%, 95% CI 70.7 – 85.5%; FABP4: AUC 71.6%, 95% CI 63.1 – 80.0%; IBP-1: AUC 73.9%, 95% CI 65.7 – 82.1%; ST2: AUC 76.2%, 95% CI 68.5 – 84.0%; EuroSCORE II: AUC 68.4%, 95% CI 59.3 – 77.5%). Conclusion This analysis has revealed novel biomarkers (CSTB, FABP4, IBP-1, ST2), which so far have not been characterized in M-TEER and suggests significant prognostic implications. Predictive performance of each of the respective biomarkers was superior to the most commonly used pre-operative risk stratification tool: the surgical EuroSCORE II. This hypothesis-generating study warrants further examination of these promising biomarkers.

Myocardial scar in end-stage hypertrophic cardiomyopathy: correlation with systolic function and prognostic significance

Abstract Background Hypertrophic cardiomyopathy with systolic impairment, often referred to as end-stage HCM (ES-HCM), has a poor prognosis. Scar is a significant contributor but the patterns and prognostic significance are unknown. Aim To understand role of scar in ES-HCM and investigate potential predictors of outcome. Methods A retrospective 4 centre study of ES-HCM (LVEF≤55%) who had undergone CMR between 2006 and 2022 for unexplained LVH. Exclusion criteria were: scaring therapies (septal reduction), phenocopies (amyloidosis, storage) and dual pathologies (severe aortic valve disease, previous infarction). CMR followed standardized protocols. All images were core-lab analysed de-novo with scar quantified using the full width at half maximum technique for late gadolinium enhancement (LGE) quantification in grams (LGEm) and percentage of total LV mass (LGE%). Cox models used to identify risk factors for all-cause mortality. Results From 3810 HCM CMR scans, 128 were ES-HCM pts (3%), 25(20%) were excluded due to known infarction. 103 (male n=82, 81%; age 57yrs[IQR51–68]) formed the study cohort. Of the 54% genotyped, 62% carried a (likely)pathogenic sarcomere mutation: MYBPC3 (n=20), MYH7 (n=7), TNNT2 (n=4), TMP1 (n=2),ALPK3 (n=1). Heart morphology was: 38(37%) isolated basal septal hypertrophy, 30(29%) reverse septal curvature, 7(7%) mid-cavity LVH with apical aneurysm, 3(3%) apical HCM, 24%other. The median EF was 46%(IQR 39-50). In only one third (34%) the ventricle was dilated (LVEDd mean 97ml/m2 IQR 79-112). The RV was impaired in 19(18%). Median max wall thickness was 17mm(IQR15-20) and LVmass 74mg/Kg(IQR65-90). Scar was present in 94(93%) and was typically extensive: median LGE% 23%(IQR 13-33), LGEm 31g(IQR 16-45) – although 7% had no scar. The LGE pattern was diffuse in 38%, patchy in 35%, ring-like in 9%, and infarct-like in 7% (all without coronary narrowing at invasive/non-invasive coronary artery assessment). LGE and cardiac function were effectively independent with low or no correlation between scar and LVEF% or global longitudinal strain (r2=0.015,p=0.227 or r2= 0.048,p=0.028 for LGE% and LGEm against LVEF; r2=0.059,p=0.021 or r2=0.196,p<0.001 for LGE% and LGEm against GLS) with poor correlation also with indexed stroke volume. During a 5 year (IQR 3-7) follow-up (516patient-years), 30 deaths occurred: mean age at death was 62(52-74). Using multivariate Cox regression analysis EF and demographics such as age were not predictive, but LGE% (HR 1.046, 95%IC 1.007-1.086, p=0.019 and GLS (HR 1.172, 95%IC 1.004-1.368, p=0.044) were independent all-cause mortality predictors (C-index 0.708; table). Conclusion Myocardial scar is almost always present in ES-HCM and is typically extensive – but with some unexpected features: 7% of patients have no LGE, dual pathology(infarction) is not rare, and ringlike LGE (ALVClike) may occur. LGE correlates poorly with any measure of LV impairment but is a strong predictor of mortality, as is GLS.

The prognostic significance of Weber and ventilatory CPET classifications in amyloidosis patients

Abstract Background Cardiopulmonary exercise testing (CPET) has emerged as an important tool for risk stratification and prognosis assessment in patients with cardiac diseases. The Weber and Ventilatory Functional Classification have been correlated with outcomes in patients with Heart Failure (HF). Weber classification is based on VO2: Weber class A, peak VO2 >20 mL/kg per minute; class B, peak VO2 16–20 mL/kg per minute; class C, peak VO2 10–16 mL/kg per minute; and class D, peak VO2 ≤10 mL/kg per minute and Ventilatory classification on VE/VCO2 slope I-IV (Figure A). Although VO2 and VE/VCO2 variables have found altered in the amyloidosis population, the applicability of this classification in a cohort of amyloidosis patients and its correlation with all-cause mortality have not been explored. Purpose To evaluate if the Weber and Ventilatory Classification of HF predicts mortality amyloidosis patients. Methods 194 with diagnosis of amyloidosis who underwent CPET from February 2010 to February 2024 were included in this retrospective cohort study. Patients with at least one CPET complete data were included in the analysis. Data on the type of amyloidosis, comorbidities, and echocardiogram were retrieved from medical records. Cohort was divided into two groups according to the Weber Classification: Weber Class A/B and Weber Class C/D. Individuals with CPET studies after heart transplant were excluded from the analysis. Statistical analyses including Fisher’s exact test, chi-square, Tukey-Kramer (TK), Cox regression model analysis, proportional hazards model for time to event, and Kaplan–Meier curves were performed. A p-value <0.05 was considered significant. Results Out of the 194 patients, 94 were classified as Weber A-B and 100 as Weber B-C. The age at stress test was similar between the groups: Weber A/B 62.9 ± 11.7 years and Weber C/D 62.3 ± 10.7 years (p=0.087). Ejection Fraction was similar between groups, 32% and 28.9% in A-B and C-D respectively (p =0.207). Higher levels of NT-proBNP were found in the Weber C/D group. The prevalence of comorbidities was balanced among the groups except chronic kidney disease, which was higher in Weber Class C/D (40%) vs (20.2%) in Weber Class A/B (Table 1). Cox analysis revealed a strong association between higher Weber class and the outcome HR 2.36 (1.18 – 4.71) p=0.014. For Higher Ventilatory Class (Group III-IV) similar results were found HR 2.95 (1.60 – 5.45) p=0.005(Table 2). Mortality was significantly higher during the follow-up in the Weber C/D group (25%) vs (10%) in the Weber A-B group p=0.007(Figure D). Conclusion Weber and ventilatory Classification based on CPET, besides predicting outcomes in patients with cardiac disease, are strong predictors of mortality in patients with amyloidosis. These findings suggest that this patient group benefits from earlier stratification to assess prognosis and the potential requirement for transplant independently from other factors.

Single spot albumin to creatinine ratio as an independent predictor of 12 years follow-up mortality in acute coronary syndromes without ST-segment elevation

Abstract Background To the best of our knowledge there is no evidence of the association between microalbuminuria, measured as single spot urine albumin to creatinine ratio (ACR), with very long-term mortality in patients with non-ST segment Elevation Acute Coronary Syndromes. Aim To evaluate the association between admission ACR and very long-term all-cause mortality in an unselected cohort of non-ST-segment elevation acute coronary syndromes patients. Methods A prospective cohort study was conducted, including patients with non-ST-segment elevation acute coronary syndromes admitted in the Intensive Care Unit. The ACR was determined in spontaneous urine samples during the first 24 hours after admission and analyzed by immunoturbidimetry. The primary endpoint was all-cause mortality during the follow-up. Actuarial survival curves were compared by log rank test and a logistical Cox regression analysis was performed to identify variables independently associated with mortality in the follow-up. Statistics were calculated using the IBM Statistics program SPSS version 26. Results 600 patients were analyzed. The overall average ACR value was 7 mg/gr (95% CI 4-26). 76% had normoalbuminuria (ACR 0-30 mg/gr), 22% had microalbuminuria (ACR 30-300 mg/gr), and 1.5% had macroalbuminuria (ACR > 300 mg/gr). The median and interquartile range of follow-up was 12 years (95% IC 11-14). The average ACR among those who met the primary endpoint was 59.15 mg/gr (95% CI 52-66) and among the survivors, 27.66 mg/gr (95 % CI 63-77), p > 0,003. ACR terciles were defined by 33th and 66th percentiles: tercile 1: patients with ACR of 0 to 4 mg/gr, tercile 2: ACR from 4 to 17 mg/g and tercile 3 values greater than 17mg/gr. Strong associations were observed between ACR with age, hypertension, stroke and history of COPD, previous use of angiotensin II converter/blocking enzyme inhibitors, systolic blood pressure at admission, ST segment deviation, left ventricle ejection fraction and elevation of serum Troponin T and CPK MB. All cause-mortality during the follow-up was 14% (CI 95% 11-17). Elevation of ACR was significantly associated with long term mortality risk: log rank test chi square: 133.936, p = 0.0001. By multivariate Cox regression analysis adjusted by age, gender, diabetes, hypertension, serum creatinine, troponin T elevation, ST segment deviation, previous AMI, prior use of aspirin, statins and percutaneous coronary intervention after hospitalization, the ACR was independently associated with a 12-year follow-up mortality: OR 13 (95% IC 5-35; p < 0.0001). Conclusion Single spot urine ACR at admission is a strong predictor of 12-year follow-up mortality in an unselected cohort of patients with non-ST-segment elevation acute coronary syndromes.Baselines characteristics of cohortsMultivariable COX regression analysis

A new prehospital cardiac risk assessment index derived from vital signs by first contact emergency medical service, including prehospital oxygen saturation, for accurate prehospital triage of acute m

Abstract Background: Rapid and accurate triage is essential to improve the prognosis of patients with severe acute myocardial infarction (AMI). However, prehospital triage using vital signs, including prehospital oxygen saturation (SpO2), by first medical contact has not been evaluated. Purpose: The purpose of this study was to develop a new risk stratification index for AMI using vital signs including SpO2 for rapid and accurate prehospital triage. Methods: From January 2013 to June 2022, 3006 AMI patients who were directly transported by ambulance were enrolled from the Mie ACS registry. Based on observed risk relationships in 3,006 AMI patients, we developed and evaluated a prehospital cardiac risk assessment index (P-CRAI) using age, heart rate, and systolic blood pressure (SBP) and SpO2 to predict 30-day mortality: (heart rate×[age/10]2)/SBP＋1.1(100-SpO2). We also analyzed whether P-CRAI predicted the need for mechanical circulatory support (MCS) or ventilator use. Results: In the receiver operating characteristic (ROC) curve analysis, P-CRAI 38.1 has a sensitivity of 84.4%, specificity of 72.7%, and accuracy of 84.3% for predicting 30-day mortality, and P-CRAI was a strong predictor of 30-day mortality compared with the other indices and variables (Figure 1A). When divided into two groups with P-CRAI 38, Kaplan-Meier survival curves showed significant differences in 30-day survival between the high and low groups (83.7% vs. 98.7%, P<0.001, Figure 1B). P-CRAI≥38 was the strongest independent predictor of 30-day mortality with a hazard ratio of 7.64 compared to the other factors by multivariate Cox regression analysis. The spline curve of 30-day mortality by P-CRAI shows a correlation with prognosis (Figure 2A). In this study, we then used the bootstrap method to generate a calibration curve and validate P-CRAI. The results showed an excellent fit and that P-CRAI accurately estimated patient prognosis (Figure 2B). In addition, P-CRAI was a robust predictor of the very early events of death at 24 hours and MCS or ventilator use by ROC curve analysis. (c-statistic 0.835 and 0.726, respectively, P<0.01). Conclusion: The P-CRAI was found to be a useful tool for prehospital triage of AMI patients, accurately predicting 30-day mortality and the need for MCS.Figure 1.Figure 2.

A novel 12-lead standard ECG derived scoring system for risk stratification in the emergency department

Abstract Background/Aims The ECG represents a routinely used diagnostic tool in the assessment of patients in the emergency department. Beside specific alterations within the ECG indicative of underlying pathologies, such as ST-elevation in myocardial infarction, several other parameters have been developed over the past decades that proofed themselves as strong and independent predictors of worsened outcome independent of a specific underlying pathology. These include basic metrics such as heart rate and QRS duration, but also more advanced biomarkers such as QRS microfragmentation (QRSµf) [1] and total cosine R to T (TCRT) [2] . In this work, we aimed to summarize all these markers derived from 12-lead standard ECGs into one novel risk score and evaluate its performance as mortality predictor in the emergency department. Methods We retrospectively collected 10- second 12- lead ECG recordings unselected patients presenting to the emergency department of a large university hospital between September 2019 and June 2022. For each patient a risk score was calculated from the first retrieved ECG using the criteria displayed in Figure 1. Calculation of all parameters was done as previously published. Patients with a total score of 0-1 points, 2-3 points, 4-6 points and 7 points were considered as low, intermediate, high and very high risk, respectively. The performance of the risk score was evaluated using Cox regression analysis and Kaplan-Meier curves with all-cause mortality within one year as primary endpoint. Results In total, 10 781 patients were included in our analyses. Median age was 69 (IQR 54-80) years, 5 588 (52%) were male and 5 193 (48%) were female. 6 966 (65%) patients were considered as low risk, 2 656 (25%) patients as intermediate risk, 1 098 (10%) patients as high risk and 61 (1%) patients as very high risk according to the ECG risk score with one year mortality rates of 8%, 17%, 26% and 43%, respectively (p < 0.001 for difference). In cox regression analysis the novel ECG risk score was a strong and independent predictor of one-year all-cause mortality with a hazard ratio of 1.35 (95% CI 1.31-1.39, p < 0.001). Kaplan-Meier survival curves for different risk categories are displayed in Figure 2. Conclusion In an unselected population of patients presenting to the emergency department of a large university hospital a novel risk score calculated from standard 12-lead ECGs recorded during clinical routine was a strong and independent mortality predictor. Further studies are needed to evaluate how incorporation of the novel score into existing triage systems can improve patient care.Figure 1:Calculation of ECG risk scoreFigure 2:Kaplan-Meier survival curves

Early coronary revascularization among stable patients with non-ST-segment elevation acute coronary syndromes: the role of diabetes and age

Abstract Background Diabetes mellitus affects 10-30% patients hospitalized with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and two-fold higher mortality risk compared to non-diabetics. Despite higher post-PCI complications in diabetic patients, guidelines advise early invasive NSTE-ACS treatment for all, based expert opinion, and limited evidence. Purpose To investigate the impact of an early coronary revascularization (<24 hours) compared with initial conservative strategy on clinical outcomes in diabetic patients with NSTE-ACS who are in stable condition at hospital admission. Methods The ISACS-TC database was queried for a sample of diabetic and nondiabetic patients with diagnosis of NSTE-ACS. Patients with cardiac arrest, hemodynamic instability, and serious ventricular arrhythmias were excluded. The characteristics between groups were adjusted using logistic regression and inverse probability of treatment weighting models. Primary outcome measure was all cause 30-day mortality. Risk ratios (RRs) and odds ratios (ORs) with their 95% CIs were employed. Results Of the 7,589 NSTE-ACS patients identified, 2,343 were diabetics. The data show a notable reduction in mortality for the elderly undergoing early revascularization compared to those receiving an initial conservative strategy both in the diabetic (3.3% versus 6.7%; RR: 0.48; 95% CI: 0.28-0.80) and nondiabetic patients (2.7% versus 4.7%: RR: 0.57; 95% CI: 0.36-0.90). In multivariate analyses, diabetes was a strong independent predictor of mortality in the elderly (OR: 1.43; 95% CI: 1.03-1.99), but not in the younger patients OR: 1.04; 95% CI: 0.53-2.06). Conclusions Early coronary revascularization does not lead to any survival advantage within 30 days from admission in young NSTE-ACS patients who present to hospital in stable conditions with and without diabetes. An early invasive management strategy may be best reserved for the elderly. Factors beyond revascularization are of considerable importance for outcome in elderly diabetic subjects with NSTE-ACS.

Clinical Correlates and Prognostic Impact of Cognitive Dysfunction in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF.

Cognitive impairment is common in patients with heart failure and preserved ejection fraction but its clinical correlates and prognostic associations are poorly understood. We analyzed cognitive function, using the Mini-Mental State Examination (MMSE), in patients with heart failure and preserved ejection fraction enrolled in a prespecified substudy of the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). Logistic regression analyses were performed to determine the variables associated with lower MMSE scores at baseline and postbaseline decline in MMSE scores at 48 weeks. Cox proportional hazards regression and semiparametric proportional rates models were used to examine the risk of clinical outcomes related to baseline MMSE scores, and decline in MMSE scores during follow-up, adjusted for prognostic variables including NT-proBNP (N-terminal pro-B-type natriuretic peptide). At baseline, cognitive function was normal (MMSE score 28-30) in 1809 of 2895 patients (62.5%), borderline (score 24-27) in 794 (27.4%), and impaired (score <24) in 292 (10.1%). Variables associated with both a lower MMSE score at baseline and a decline in score from baseline included older age, a history of stroke or transient ischemia attack, and lower serum albumin. Compared with those with baseline MMSE scores of 28 to 30, patients in the lower MMSE score categories had a stepwise increase in the risk of the composite of time to first HF hospitalization or cardiovascular death, with an adjusted hazard ratio of 1.27 (95% CI, 1.06-1.53) for those with scores of 24 to 27 and 1.58 (95% CI, 1.21-2.06) for those with scores <24, respectively. These associations were also found for the individual components of the composite and all-cause death. Likewise, cognitive impairment was associated with a 50% higher risk of total (first and repeat) heart failure hospitalizations and cardiovascular deaths. Examining the change in MMSE score from baseline, a decrease in MMSE score during follow-up was associated with a higher risk of death. In patients with heart failure and preserved ejection fraction, even modest baseline impairment of cognitive function was associated with worse outcomes, including death. A decline in MMSE score during follow-up was a strong predictor of mortality, independent of other prognostic variables.

Elevated Cardiac Troponin Levels as a Predictor of Increased Mortality Risk in Non-Cardiac Critically Ill Patients Admitted to a Medical Intensive Care Unit.

Background: Cardiac troponin I (TnI) is a specific marker of myocardial damage used in the diagnosis of acute coronary syndrome (ACS). TnI levels can also be elevated in patients without ACS, which is linked to a worse prognosis and mortality. We evaluated the clinical implications and prognostic significance of serum TnI levels in critically ill non-cardiac patients admitted to the intensive care unit (ICU) at a tertiary-level hospital. Materials and Methods: A three-year retrospective study including the years 2017-2020 was conducted to evaluate in-hospital mortality during ICU stay and mortality rates at 28 and 90 days, as well as one and two years after admission, in 557 patients admitted to the medical ICU for non-cardiac causes. Results: TnI levels were elevated in 206 (36.9%) patients. Patients with elevated TnI levels were significantly older and had higher rates of comorbidities, including chronic heart failure, coronary heart disease, and chronic kidney disease (p < 0.05 for all). Patients with elevated TnI levels required more invasive mechanical ventilation, vasopressor infusion, and dialysis in the ICU and experienced more shock within the first 72 h (p = 0.001 for all). High TnI levels were associated with higher Acute Physiological and Chronic Health Evaluation (APACHE) II (27.6 vs. 20.3, p = 0.001) and Sequential Organ Failure assessment (8.8 vs. 5.26, p = 0.001) scores. Elevated TnI levels were associated with higher mortality rates at 28 days (58.3% vs. 19.4%), 90 days (69.9% vs. 35.0%), one year (78.6% vs. 46.2%), and two years (82.5% vs. 55.6%) (p < 0.001 for all). Univariate logistic regression analysis revealed that high TnI levels were a strong independent predictor of mortality at all time points: 28 days (OR = 1.2, 95% CI: 1.108-1.3, p < 0.001), 90 days (OR = 1.207, 95% CI: 1.095-1.33, p = 0.001), one year (OR = 1.164, 95% CI: 1.059-1.28, p = 0.002), and two year (OR = 1.119, 95% CI: 1.026-1.22, p = 0.011). Multivariate analysis revealed that age, albumin level, APACHE II score, and requirements for dialysis and vasopressor use in the ICU were important predictors of mortality across all timeframes, but elevated TnI levels were not. Conclusions: Elevated TnI levels in critically ill non-cardiac patients are markers of disease severity. While elevated TnI levels were significant predictors of mortality in the univariate analysis, they lost significance in the multivariate model when adjusted for other factors. Patients with elevated TnI levels had higher mortality rates across all timeframes, from 28 days to two years.

Accuracy of smartwatches for the remote assessment of exercise capacity

Exercise capacity is a strong independent predictor of cardiovascular and all-cause mortality. The utilization of well-established submaximal tests of exercise capacity such as the 6-min walk test (6MWT), 3-min step test (3MST) and 10-chair rise test (10CRT) in the community would improve patient care but requires remote monitoring technology. Consumer grade smartwatches provide such an opportunity, however, their accuracy in measuring physiological responses to these tests is unclear. The aim of this study was to determine the accuracy of consumer grade smartwatches in assessing exercise capacity to develop a framework for remote, unsupervised testing. 16 healthy adults (7 male (44%), age median 27 [interquartile range (IQR) 26,29] years) performed 6MWTs using two protocols: (1) standard—straight 30 m laps (6MWT-standard) and 2) continuous lap—circular 240 m laps around a park (6MWT-continuous lap), 3MSTs and 10CRTs. Each one of these four tests was performed three times across two clinic visits. Each participant was fitted with a Garmin Vivoactive4 and Fitbit Sense smartwatch to measure three parameters: distance, step counts and heart rate (HR) response. Reference measures were a meter-wheel, hand tally counter and ECG, respectively. Mean HR was measured at rest, peak exercise and recovery. Agreement was measured using Bland–Altman analysis for repeated measures and summarized as median absolute percentage errors (MAPE). Distance during 6MWT-continuous lap had better agreement than during 6MWT-standard for both Garmin (MAPE: 6.4% [3.0, 10.4%] versus 20.1% [13.9, 28.4%], p < 0.001) and Fitbit (8.0% [2.9, 10.1% versus 18.8% [15.2, 28.1%], p < 0.001). Garmin measured step count more accurately than Fitbit (MAPE: 1.8% [0.9, 2.9%] versus 8.0% [2.6, 12.3%], p < 0.001). Irrespective of test, both devices showed excellent accuracy in measuring HR at rest and recovery (≤ 3%), while accuracy decreased during peak exercise (Fitbit: ~ 12% and Garmin: ~ 7%). In young adults without mobility difficulties, exercise capacity can be measured remotely using standardized tests and consumer grade smartwatches.

Prospective Variation of Cytokine Trends during COVID-19: A Progressive Approach from Disease Onset until Outcome

COVID-19 is characterized by pronounced hypercytokinemia. The cytokine switch, marked by an imbalance between pro-inflammatory and anti-inflammatory cytokines, emerged as a focal point of investigation throughout the COVID-19 pandemic. However, the kinetics and temporal dynamics of cytokine release remain contradictory, making the development of new therapeutics difficult, especially in severe cases. This study collected serum samples from SARS-CoV-2 infected patients at 72 h intervals and monitored them for various cytokines at each timepoint until hospital discharge or death. Cytokine levels were analyzed based on time since symptom onset and patient outcomes. All cytokines studied prospectively were strong predictors of mortality, particularly IL-4 (AUC = 0.98) and IL-1β (AUC = 0.96). First-timepoint evaluations showed elevated cytokine levels in the mortality group (p &lt; 0.001). Interestingly, IFN-γ levels decreased over time in the death group but increased in the survival group. Patients who died exhibited sustained levels of IL-1β and IL-4 and increased IL-6 levels over time. These findings suggest cytokine elevation is crucial in predicting COVID-19 mortality. The dynamic interplay between IFN-γ and IL-4 highlights the balance between Th1/Th2 immune responses and underscores IFN-γ as a powerful indicator of immune dysregulation throughout the infection.

Prognostic value of the duke activity Status Index Questionnaire in predicting mortality in patients with chronic heart failure: 36-month follow-up study

BackgroundThe Duke Activity Status Index (DASI) questionnaire has been the focus of numerous investigations - its discriminative and prognostic capacity has been continuously explored, supporting its use in the clinical setting, specifically during rehabilitation in patients with chronic heart failure (CHF).However, studies exploring optimal DASI questionnaire threshold scores are limited.ObjectiveTo investigate optimal DASI questionnaire thresholds values in predicting mortality in a CHF cohort and assess mortality rates based on the DASI questionnaire using a thresholds values obtained.MethodologyThis is a prospective cohort study with a 36-month follow-up in patients with CHF. All patients completed a clinical assessment, followed by DASI questionnaire, pulmonary function, and echocardiography. The Receiver Operating Characteristic (ROC) curve analysis was used to discriminate the DASI questionnaire score in determining the risk of mortality. For survival analysis, the Kaplan-Meier model was used to explore the impact of ≤/>23 points on mortality occurring during the 36-month follow-up.ResultsOne hundred and twenty-four patients were included, the majority being elderly men. Kaplan Meier analysis revealed that ≤/> 23 was a strong predictor of CHF mortality over a 36-month follow-up.ConclusionA score of ≤/>23 presents good discriminatory capacity to predict mortality risk in 36 months in patients with CHF, especially in those with reduced or mildly reduced ejection fraction. Age, ejection fraction, DASI questionnaire score and use of digoxin are risk factors that influence mortality in this population.

Correlation of Serum Lactate and Shock Index as Mortality Predictor in Polytrauma Patients

In polytrauma patients, serum lactate and hypovolemic shock are critical biomarkers for prognosis and treatment guidance. Elevated lactate levels indicate tissue hypoperfusion and anaerobic metabolism, often correlating with increased mortality. Objective: To analyze the correlation between serum lactate levels and shock index as predictors of in-hospital mortality in polytrauma patients. Methods: A Cohort study was conducted from August 2022 to July 2023 at a single tertiary care hospital in Karachi. Patients were chosen via consecutive sampling techniques and included adult patients with polytrauma injuries (ISS ≥ 15) who survived at least 24 hours. Patients with a history of diabetes were excluded. The serum lactate levels and shock index at the time of admission and over the first 24 hours were the exposures while in-hospital mortality, was the primary outcome. Statistical analyses were conducted using Stata 16.0. Categorical variables were analyzed using the chi-square test. Multivariable logistic regression evaluated mortality risk, adjusting for age, ISS, and shock index. Results: The in-hospital mortality rate in the study was 6.4% with significant predictors of mortality included increasing age (47.05 vs. 27.62 years, p&lt;0.001), higher Injury Severity Scores (ISS) (24 vs. 19, p= 0.02), and elevated shock index at admission (0.84 vs. 0.71, p&lt;0.001). Lactate metrics were strongly associated with mortality, showing significant correlations. Conclusions: Higher serum lactate levels and shock index are strong predictors of mortality in polytrauma patients. Greater age and injury severity also contribute to poorer outcomes.

Physician–patient racial concordance and newborn mortality

The racial gap in infant mortality is a pressing public-health concern, and [B. N. Greenwood et al., Proc. Natl. Acad. Sci. U.S.A. 117, 21194-21200 (2020), 10.1073/pnas.1913405117] suggest that Black newborns are more likely to survive if cared for by Black physicians after birth, even in models that control for numerous variables, including hospital and physician fixed effects, and the 65 most common comorbidities affecting newborns (as described by International Classification of Disease codes). We acquired the data used in the study, covering Florida hospital discharges from 1992 through the third quarter of 2015, to replicate and extend the analysis. We find that the magnitude of the concordance effect is substantially reduced after controlling for diagnoses indicating very low birth weight (<1,500 g), which are a strong predictor of neonatal mortality but not among the 65 most common comorbidities. In fact, the estimated effect is near zero and statistically insignificant in the expanded specifications that control for very low birth weight and include hospital and physician fixed effects.

Differential prognostic value of residual nodal burden in breast cancer subtypes.

Residual cancer burden (RCB) index after neoadjuvant chemotherapy (NAC) is highly prognostic in patients with breast cancer (BC) but does not account for subtype or the precise impact of residual nodal burden (RNB). We aimed to precisely define the effect of RNB on survival by subtypes. Adult women with non-metastatic BC diagnosed from 2006 to 2021 in the National Cancer Database (NCDB) who received NAC followed by surgery within 8months were included. RNB was also evaluated as a predictor of mortality with multivariable logistic regression. Kaplan-Meier analyses were performed to compare overall survival. 51,917 patients were included. After adjustment, ypN stage was the strongest predictor of mortality, with an odds ratio (OR) of 2.24 (95% CI 2.08-2.41) for ypN1 vs ypN0 and increased with increasing nodal burden-ypN2 vs ypN0 OR 5.03, 95% CI 4.60-5.51 and ypN3 vs ypN0 OR 8.85, 95% CI 7.88-9.93. Stratification of survival curves with higher RNB is most pronounced for triple-negative breast cancer (TNBC) with an absolute difference of 64% in 5-year overall survival between ypN0 and ypN3 patients, and lowest for the ER+/HER2- subtype with a 25% absolute difference in 5-year OS between ypN0 and ypN3 patients. On interaction analysis, ypN status was a stronger predictor of mortality for the TNBC subtype compared to other subtypes. RNB has a significantly different impact on survival by BC subtypes. Future study of optimal therapeutic strategies for patients with residual nodal disease after NAC should account for subtype-specific differences in prognosis.