Death Curves Research Articles

Lower early mortality after acute pulmonary embolism in patients with WHO-defined obesity: results from a post-hoc cohort analysis with external validation

Abstract Background The relationship between obesity, defined as a Body Mass Index (BMI) ≥ 30 kg/m2, and mortality in venous thrombo-embolism remains controversial. Objectives To compare early outcomes after pulmonary embolism (PE) between obese patients, and non-obese, non-underweight patients. Methods We performed a post-hoc analysis based on prospectively recorded individual patient data from the multicenter BFC-FRANCE registry. We compared rates of outcomes using multivariable logistic regression or a Cox model for 30-day and 6-month outcomes respectively. We assessed the incremental value of adding BMI information on top of the 30-day European Society of Cardiology (ESC) prognostic algorithm. Results A total of 2,390 patients with a BMI ≥ 18.5 kg/m2 (mean age, 66.9±16.8 years; 1,188 men [49.7%]) were included, 686 patients [28.7%] in the obese group, and 1,704 patients [71.3%] in the non-obese group. Mortality rates were significantly lower in obese patients versus non-obese patients at 30 days (OR, 0.59; 95% CI, 0.35-0.98), and 6 months. Cox-model-derived adjusted curves for all-cause death at 6 months, with hazard ratios (HRs) between obese and non-obese patients, after acute PE, are shown in the Figure. Rates of secondary non-fatal outcomes (including recurrent VTE) did not differ between groups. The addition of the obesity information on top of the ESC prognostic model improved global model fit, and discriminatory and calibration capacities, yielding significant reclassification based on the observed mortality rates with the ESC model as reference. Findings were confirmed in an external validation using 35,796 PE patients from the RIETE registry. Conclusion We present evidence indicating lower early and mid-term mortality after PE in patients classified as obese based on BMI, compared with non-obese, non-underweight patients. BMI should likely be incorporated into algorithms or scoring systems for predicting early mortality following PE.

Association of left ventricular ejection fraction improvement with prognosis in patients with cardiac sarcoidosis: insights from the ILLUMINATE-CS study

Abstract Introduction While the beneficial impact of enhancing left ventricular ejection fraction (LVEF) is well-documented in patients with heart failure with reduced LVEF, its relevance in cardiac sarcoidosis (CS) remains unclear. Purpose This study aimed to identify predictive factors for LVEF improvement and explore its association with prognosis in patients with CS. Methods A post-hoc analysis of the ILLUMINATE-CS registry, a retrospective observational study across multiple centers, was conducted. CS diagnosis adhered to either the 2016 Japanese Circulation Society guidelines or the 2014 Heart Rhythm Society expert consensus statement. Patients with baseline LVEF ≥50% were excluded in the current analysis. LVEF improvement was quantified as the variance between baseline and follow-up echocardiography. Patients were categorized into tertiles based on LVEF improvement: 1st tertile (≤0%, least improved), 2nd tertile (0–9%), and 3rd tertile (>9%, most improved) groups. The primary outcome was all-cause mortality after follow-up echocardiography. Results Among 188 enrolled patients (mean age 62.1±10.7 years; 42.6% male), 65, 60, and 63 were allocated to the 1st, 2nd, and 3rd tertile groups, respectively. Multivariate linear regression analysis revealed that narrower QRS duration, lower baseline LVEF, and absence of beta-blocker prescription at baseline were independently associated with greater LVEF improvement. Over a median follow-up of 407 days, 26 all-cause deaths occurred. Kaplan–Meier curves exhibited significant difference among the tertile groups (log-rank, P=0.002). Cox proportional hazard analysis, adjusted for possible prognostic factors including LVEF, demonstrated significantly higher mortality in the 1st and 2nd tertile groups compared to the 3rd tertile group (vs. 1st tertile: hazard ratio [HR] 22.14, 95% confidence interval [CI] 2.73–179.50, P=0.004; vs. 2nd tertile: HR 8.17, 95% CI 1.02–65.71, P=0.048). Additionally, treating LVEF improvement as a continuous variable revealed an independent association with increased mortality (LVEF improvement per 5%: HR 0.69, 95% CI 0.54–0.87, P=0.002). Conclusions Improvement LVEF in patients with CS is significantly associated with improved outcomes, highlighting its clinical importance in managing CS.Kaplan–Meier curves for all-cause death

One-year outcomes of patients with hypertrophic cardiomyopathy according to levels of inflammatory biomarkers

Abstract Background Hypertrophic cardiomyopathy (HCM) is a vastly heterogeneous sarcomere disorder unified by maximal left ventricular (LV) thickness increases. The lifetime relative risk of morbidity in HCM is four-fold higher than in the general population, primarily driven by arrhythmias and heart failure (HF). Numerous prognostic features have been identified, but our ability to identify high-risk patients of progression remains rudimentary. Small retrospective studies have shown that systemic inflammation is associated with adverse outcomes in patients with HF; others, small and single-center, have also shown associations between adverse outcomes and inflammation in HCM. Purpose We aimed to determine whether elevated levels of inflammatory biomarkers are associated with an increased risk of acute heart failure (AHF) and mortality at 1 year in a large cohort of patients with HCM across multiple centers in the United States (US). Methods In this retrospective study, using the US cohort of 60 healthcare organizations in the TriNetX database, we included more than 85,000 adult patients with HCM (ICD-10-CM codes I42.1 and I42.2) between 2004 and 2024. Patients were divided according to predetermined cut-offs of different inflammatory biomarkers (C-reactive protein [CRP], <2 mg/L vs. 2-100 mg/L; white blood cells [WBC], < vs. ≥ the median [8x10^3/µL]; neutrophils [Neu], < vs. ≥ the median [5x10^3/µL]). These cohorts were then 1:1 propensity score matched (PSM) for age, sex, and race. We used Kaplan-Meier survival curves to derive cumulative incidence curves (as 1 minus Kaplan-Meier survival estimates) for AHF (ICD-10-CM codes I50.21, I50.23, I50.31, I50.33, I50.41, I50.43) or death, and we compared them with the Log-rank (Mantel-Cox) test. We also derived Hazard Ratios (HR) with 95% Confidence Interval (CI) from Cox regression analysis to compare the outcomes within the groups at 1-year. Results After PSM, patients with HCM and CRP levels between 2-100 mg/L experienced higher rates of the composite outcome (19.6% vs. 12.2%, Log-rank p<0.001; HR 1.67, 95% CI [1.29-2.16]), as well as the separate outcomes of death (14.7% vs. 6.8%, Log-rank p<0.001; HR 2.23, 95% CI [1.68-2.98]) and AHF (10.9% vs. 7.5%, Log-rank p<0.001; HR 1.49, 95% CI [1.07-2.07]), compared to those with CRP <2 mg/L (Table 1)(Figure 1). Similarly, patients with Neu ≥5x10^3/µL reported higher incidences of the composite outcome (20.3% vs. 13.2%, Log-rank p<0.001; HR 1.62, 95% CI [1.55-1.68]) and the separates outcomes, compared to those with Neu <5x10^3/µL (Table 1) (Figure 1). Patients with WBC ≥8x10^3/µL also had increased rates of the composite outcome (19.4% vs. 14.1%, Log-rank p<0.001; HR 1.43, 95% CI [1.38-1.48]) and the separate outcomes, compared to those with WBC <8x10^3/µL (Table 1)(Figure 1). Conclusions In the first large 'real world' analysis of patients with HCM, elevated levels of inflammatory biomarkers were associated with worse outcomes of death and acute heart failure.

Flow adjusted predicted prosthesis patient mismatch in patients undergoing transcatheter aortic valve implantation

Abstract Background Effective orifice area (EOA) is flow dependent. However, established methods for the assessment of prosthesis-patient mismatch (PPM) do not consider flow status, and therefore may underestimate the rate and impact of PPM in patients with abnormal flow status. Objectives To investigate the clinical impact of flow-adjusted predicted PPM in patients undergoing transcatheter aortic valve implantation (TAVI). Methods Patients undergoing TAVI in a prospective TAVI registry were stratified by the presence of moderate or severe PPM (EOA index to body surface area [EOAi]: 0.65-0.85 or ≤0.65 and 0.55-0.70 or ≤0.55 cm2/m2 if obese). PPM was defined according to echocardiographically measured EOAi (measured PPM) or unadjusted or flow-adjusted predicted EOAi. Predicted EOAs were based on reference values of EOA for each valve generation and size (predicted PPMTHV) or native aortic annulus dimension (predicted PPMCT). Results Among 1,510 patients included (August 2007-June 2022), rates of moderate or severe PPM differed according to method of assessment; 27.0% and 8.7% according to measured PPM, 11.3% and 1.2% according to predicted PPMTHV, 12.0% and 0.1% according to PPMCT, 21.6% and 0.2% according to flow-adjusted predicted PPMTHV, and 25.1% and 0.4% according to flow-adjusted predicted PPMCT. Five-year mortality was comparable in patients with and without flow-adjusted predicted PPM defined by either method. These results were consistent when patients were stratified by flow status. Conclusions Rates of PPM differ considerably when flow status is considered. There was no consistent signal of increased risk of adverse events up to 5 years in patients with flow-adjusted predicted PPM.Frequency of PPM afteer TAVICumulative event curves for death

Características de la mortalidad por COVID-19 durante y después de la pandemia en el Perú

Introduction. The COVID-19 emergency caused a pandemic with a great impact on mortality in Peru. Objective. To analyze the magnitude of mortality due to COVID-19 and identify some sociodemographic characteristics. Methods. A descriptive ecological study was carried out, analyzing data on deaths due to COVID-19 during the period 2020-2023, as well as publicly accessible socioeconomic and demographic indicators. The variables included in the study were: year of death, number of deaths, sex, age group, province of origin, natural region, macroregion, human development index (HDI), unmet basic needs (UBN) and population density. Results. 220,628 deaths due to COVID-19 were reported, of which 219,374 (99.43%) occurred during the pandemic and 1,254 (0.57%) in the post-pandemic period; The cumulative mortality rate was 6.76 deaths/1000 inhabitants. The COVID-19 death curve shows that between 2020-2023, five waves occurred, with the second wave having the highest mortality, followed by the first wave. Mortality predominated in men, older adults (69.77%) and adults (28.11%). The macroregion of Metropolitan Lima and Callao had the highest mortality rates with 9.36 deaths/1000 inhabitants. The provinces with the highest cumulative mortality rates were those located on the coast, in quintiles with less NBI, in quintiles with a higher HDI and in those provinces with a higher population density. Conclusions. The COVID-19 pandemic caused high mortality in Peru, being higher in males, older adults, from coastal cities, with higher population density and better socioeconomic indicators.

One-year effectiveness and safety outcomes of edoxaban treatment in Chinese patients with atrial fibrillation: First snapshot of more than 4,800 patients from the ETNA-AF-China study

Abstract Background Direct oral anticoagulants (DOACs) have become the first-line therapy for ischaemic stroke prevention in atrial fibrillation (AF) patients. Data on the effectiveness and safety of single DOAC in large Chinese populations are scarce. Purpose We firstly present the one-year outcome data of edoxaban treatment in 5001 Chinese AF patients. Methods This is a multi-centre, prospective, observational study, ETNA-AF-China, conducted in 89 centres from four economic regions in Mainland of China with a follow-up of two years. Primary endpoint of safety [bleeding events including intracranial hemorrhage (ICH), all-cause and cardiovascular (CV) mortality] and efficacy endpoints [stroke, systemic embolic events (SEE), transient ischemic attack (TIA)] were adjudicated. Annualised event rates and Kaplan­Meier (KM) survival curves are given. Results A total of 4822 patients (57.1% male) using edoxaban (60 mg OD: n=2614, 30 mg OD: n=2208) who completed one-year follow-up were included in the full analysis set. The mean (SD) age of the overall patient population was 70.3 (9.5) years, CHA2DS2-VASc and HAS-BLED scores were 2.9 (1.4), 1.7 (1.0), with creatinine clearance (CrCl) of 71.2 (27.7) mL/min. Patients receiving 30 mg OD edoxaban at baseline were older (73.4 vs 67.7 years), with higher CHA2DS2-VASc score (3.3 vs 2.6), larger percentage of frail (9.9% vs 3.4%), and higher renal impairment (defined as CrCl ≤80 mL/min, 70.3% vs 42.9%). Annualised rates for all-cause and cardiovascular death in the overall population were very low with 2.22%/year and 0.41%/year, respectively. (Figure 1) The death rates were nearly three times lower in those receiving standard dose (60 mg) than reduction dose (30 mg) of edoxaban. Annualised event rates for all stroke/SEE (1.03%/year) and ischemic stroke (0.60%/year) were similar between two dose groups. Overall, annualised rates for major bleeding (1.03%/year), ICH (0.18%/year), major gastrointestinal (GI) bleeding (0.48%/year) events were relatively low, and those on 60 mg dose experienced less above bleeding events. Cumulative survival analysis demonstrated a slow increase in time-to-first event curve of all-cause death; and from baseline to 1-year follow-up, significant lower events of all-cause death (log-rank p<0.001), major bleeding (p=0.002) in 60 mg vs 30 mg edoxaban groups. (Figure 2). Conclusion Low incidences of major bleeding, notably ICH, major GI bleeding, and CV death were observed in unselected 4822 patients with AF during 1-year of edoxaban treatment. These findings confirm the effectiveness and safety of routine edoxaban use in China, consistent with other countries, and reinforce the results of the ENGAGE AF-TIMI 48 trial.Figure 1Figure 2

The Synthetic Peptide LyeTx I mn∆K, Derived from Lycosa erythrognatha Spider Toxin, Is Active against Methicillin-Resistant Staphylococcus aureus (MRSA) In Vitro and In Vivo.

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8-16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

Disparities in Survival Outcomes Between Locally Advanced Cervical Squamous Cell Carcinoma and Adenocarcinoma Treated with Chemoradiotherapy.

To determine the disparities in survival outcomes between stage IIB-IVA cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) treated with chemoradiotherapy. Patients diagnosed between 2004 and 2015 were retrospectively included from the Surveillance, Epidemiology, and End Results databases. Propensity score matching (PSM) was used in this study. The primary endpoints were cervical cancer-specific survival (CCSS) and overall survival (OS). A total of 2752 patients were identified, including 87.5% (n=2408) were SCC and 12.5% (n=344) were AC. Patients with AC had inferior 5-year CCSS (67.5% vs 54.8%, P<0.001) and OS (58.4% vs 47.2%, P<0.001) compared to those with the SCC subtype. The hazard curve of cervical cancer-related death in AC peaked at 2 years (19%) and still small peaks in the 7 and 11 years of follow-up. Regarding SCC, cervical cancer-related deaths peaked at 2 years (15%) and the hazard rate was 2.0% during the six years of follow-up. The multivariate Cox regression analyses indicated that histology was an independent prognostic factor associated with survival outcomes. Patients with AC had significantly poor CCSS (P<0.001) and OS (P<0.001). Similar results were found after PSM. Our study demonstrates a significantly better prognosis for cervical SCC patients compared to those with cervical AC undergoing chemoradiotherapy. These results highlight the importance of histological subtyping in predicting treatment outcomes and tailoring therapeutic strategies.

The Gastric Cancer Immune Prognostic Score (GCIPS) Shows Potential in Predicting an Unfavorable Prognosis for Gastric Cancer Patients Undergoing Immune Checkpoint Inhibitor Treatment.

(1) Background: This study aims to explore the predictive capability of the Gastric Cancer Immune Prognostic Score (GCIPS) for an unfavorable prognosis in gastric cancer patients undergoing immune checkpoint inhibitor (ICI) treatment. (2) Methods: This study included 302 gastric cancer patients who underwent treatment with ICIs at our institution from January 2017 to December 2022. The patients were randomly divided into a test set (201 cases) and a validation set (101 cases) using a random number table. Kaplan-Meier survival analysis and the log-rank test were used to investigate survival differences. Cox regression analysis and Lasso regression analysis were employed to establish the GCIPS and identify independent prognostic indicators. ROC curves, time-ROC curves, and nomograms were utilized to further explore the predictive performance of GCIPS. (3) Results: The test set and validation set showed no statistical differences in clinical and pathological features, as well as blood parameters (all p > 0.05). Cox regression analysis revealed that white blood cells (WBC), lymphocytes (LYM), and the international normalized ratio (INR) emerged as independent prognostic blood indicators after eliminating collinearity through Lasso analysis. The GCIPS was established using β coefficients with the following formula: GCIPS = WBC (109/L) × 0.071 - LYM (109/L) × 0.375 + INR × 2.986. ROC curves based on death and time-ROC curves demonstrated that the GCIPS had higher AUCs than other classical markers at most time points. Survival analyses of all subgroups also revealed a significant correlation between the GCIPS and patients' progression-free survival (PFS) and overall survival (OS) (all p < 0.05). Furthermore, the GCIPS was identified as an independent prognostic factor for both PFS and OS. Analyses in the validation set further confirmed the reliability and stability of the GCIPS in predicting patient prognosis. Finally, nomograms incorporating the GCIPS exhibited high accuracy in both the test and validation sets. Additionally, the nomograms revealed that the GCIPS had a higher prognostic value than any other factor, including the TNM stage. (4) Conclusions: The GCIPS demonstrated its ability to predict adverse outcomes in gastric cancer patients undergoing ICIs treatment and had a high prognostic value. As a readily accessible and simple novel biomarker, it effectively identified high-risk patients.

Novel tumor marker index using carcinoembryonic antigen and carbohydrate antigen 19-9 is a significant prognostic factor for resectable colorectal cancer

We evaluated the usefulness of a newly devised tumor marker index (TMI), namely, the geometric mean of normalized carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), in determining colorectal cancer (CRC) prognosis. This retrospective cohort study included 306 patients with stages I–III CRC who underwent elective laparoscopic resection between April 2010 and March 2020. Survival rates and risk factors of relapse-free survival (RFS) and cancer-specific survival (CSS) were analyzed using Kaplan–Meier curves and Cox proportional hazards model. High-TMI group (122 patients) had significantly lower rates (95% confidence interval [95% CI]) for 5-year RFS (89.7%, 83.9–93.5 vs. 65.8%, 56.3–73.8, p < 0.001) and CSS (94.9%, 89.4–97.6 vs. 77.3%, 67.7–84.4, p < 0.001) than low-TMI group. Multivariate analysis (hazard ratio [95% CI]) indicated ≥ T3 disease (RFS: 2.69, 1.12–6.45, p = 0.026; CSS: 7.64, 1.02–57.3, p = 0.048), stage III CRC (RFS: 3.30, 1.74–6.28, p < 0.001; CSS: 6.23, 2.04–19.0, p = 0.001), and high TMI (RFS: 2.50, 1.43–4.38, p = 0.001; CSS: 3.80, 1.63–8.87, p = 0.002) as significant RFS and CSS predictors. Area under the curve (AUC) of 5-year cancer deaths (0.739, p < 0.001) was significantly higher for TMI than for CEA or CA19-9 alone. Preoperative TMI is a useful prognostic indicator for patients with resectable CRC.

Development and Validation of a Risk Score Predicting Death Without Transplant in Adult Heart Transplant Candidates

The US heart allocation system prioritizes medically urgent candidates with a high risk of dying without transplant. The current therapy-based 6-status system is susceptible to manipulation and has limited rank ordering ability. To develop and validate a candidate risk score that incorporates current clinical, laboratory, and hemodynamic data. A registry-based observational study of adult heart transplant candidates (aged ≥18 years) from the US heart allocation system listed between January 1, 2019, and December 31, 2022, split by center into training (70%) and test (30%) datasets. Adult candidates were listed between January 1, 2019, and December 31, 2022. A US candidate risk score (US-CRS) model was developed by adding a predefined set of predictors to the current French Candidate Risk Score (French-CRS) model. Sensitivity analyses were performed, which included intra-aortic balloon pumps (IABP) and percutaneous ventricular assist devices (VAD) in the definition of short-term mechanical circulatory support (MCS) for the US-CRS. Performance of the US-CRS model, French-CRS model, and 6-status model in the test dataset was evaluated by time-dependent area under the receiver operating characteristic curve (AUC) for death without transplant within 6 weeks and overall survival concordance (c-index) with integrated AUC. A total of 16 905 adult heart transplant candidates were listed (mean [SD] age, 53 [13] years; 73% male; 58% White); 796 patients (4.7%) died without a transplant. The final US-CRS contained time-varying short-term MCS (ventricular assist-extracorporeal membrane oxygenation or temporary surgical VAD), the log of bilirubin, estimated glomerular filtration rate, the log of B-type natriuretic peptide, albumin, sodium, and durable left ventricular assist device. In the test dataset, the AUC for death within 6 weeks of listing for the US-CRS model was 0.79 (95% CI, 0.75-0.83), for the French-CRS model was 0.72 (95% CI, 0.67-0.76), and 6-status model was 0.68 (95% CI, 0.62-0.73). Overall c-index for the US-CRS model was 0.76 (95% CI, 0.73-0.80), for the French-CRS model was 0.69 (95% CI, 0.65-0.73), and 6-status model was 0.67 (95% CI, 0.63-0.71). Classifying IABP and percutaneous VAD as short-term MCS reduced the effect size by 54%. In this registry-based study of US heart transplant candidates, a continuous multivariable allocation score outperformed the 6-status system in rank ordering heart transplant candidates by medical urgency and may be useful for the medical urgency component of heart allocation.

Impact of stress hyperglycemia ratio, derived from glycated albumin or hemoglobin A1c, on mortality among ST-segment elevation myocardial infarction patients

BackgroundStress hyperglycemia ratio (SHR), associated with adverse outcomes in patients with ST-segment elevation myocardial infarction (STEMI), has several definitions. This study aims to assess the prognostic value of SHR, derived from hemoglobin A1c (HbA1c) or glycated albumin (GA), to mortality.MethodsThe study comprised 1,643 STEMI patients who underwent percutaneous coronary intervention (PCI) in two centers. SHR1 was calculated using fasting blood glucose (FBG)/GA, while SHR2 was calculated using the formula FBG/(1.59*HbA1c-2.59). The primary endpoints were in-hospital death and all-cause mortality, with a median follow-up duration of 1.56 years.ResultsHigher SHR1 and SHR2 values are associated with increased risks of in-hospital death and all-cause mortality. Each standard deviation increase in SHR1 corresponded to a 39% and 22% escalation in in-hospital death and all-cause mortality, respectively. The respective increases for SHR2 were 51% and 26%. Further examinations validated these relationships as linear. Additionally, the areas under the curve (AUC) for in-hospital death were not significantly different between SHR1 and SHR2 (p > 0.05). Incorporating SHR1 or SHR2 into the base model significantly improved the discrimination and risk reclassification for in-hospital and all-cause mortality. A subgroup analysis revealed that the effects of SHR1 and SHR2 were more pronounced in patients with hypercholesteremia.ConclusionSHR1 and SHR2 have emerged as robust and independent prognostic markers for STEMI patients undergoing PCI. The SHR calculation based on either HbA1c or GA can provide additional predictive value for mortality beyond traditional risk factors, helping to identify high-risk STEMI patients.

Clinical Outcome Prediction of Early Brain Injury in Aneurysmal Subarachnoid Hemorrhage: the SHELTER-Score

BackgroundDespite intensive research on preventing and treating vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage (aSAH), mortality and morbidity rates remain high. Early brain injury (EBI) has emerged as possibly the major significant factor in aSAH pathophysiology, emphasizing the need to investigate EBI-associated clinical events for improved patient management and decision-making. This study aimed to identify early clinical and radiological events within 72 h after aSAH to develop a conclusive predictive EBI score for clinical practice.MethodsThis retrospective analysis included 561 consecutive patients with aSAH admitted to our neurovascular center between 01/2014 and 09/2022. Fourteen potential predictors occurring within the initial 72 h after hemorrhage were analyzed. The modified Rankin Scale (mRS) score at 6 months, discretized to three levels (0–2, favorable; 3–5, poor; 6, dead), was used as the outcome variable. Univariate ordinal regression ranked predictors by significance, and forward selection with McFadden’s pseudo-R2 determined the optimal set of predictors for multivariate proportional odds logistic regression. Collinear parameters were excluded, and fivefold cross-validation was used to avoid overfitting.ResultsThe analysis resulted in the Subarachnoid Hemorrhage Associated Early Brain Injury Outcome Prediction score (SHELTER-score), comprising seven clinical and radiological events: age (0–4 points), World Federation of Neurosurgical Societies (0–2.5 points), cardiopulmonary resuscitation (CPR) (2 points), mydriasis (1–2 points), midline shift (0.5–1 points), early deterioration (1 point), and early ischemic lesion (2 points). McFadden’s pseudo-R2 = 0.339, area under the curve for death or disability 0.899 and 0.877 for death. A SHELTER-score below 5 indicated a favorable outcome (mRS 0–2), 5–6.5 predicted a poor outcome (mRS 3–5), and ≥ 7 correlated with death (mRS 6) at 6 months.ConclusionsThe novel SHELTER-score, incorporating seven clinical and radiological features of EBI, demonstrated strong predictive performance in determining clinical outcomes. This scoring system serves as a valuable tool for neurointensivists to identify patients with poor outcomes and guide treatment decisions, reflecting the great impact of EBI on the overall outcome of patients with aSAH.

Triglyceride glucose index, a novel marker of insulin resistance, predicts outcomes in patients with heart failure with preserved ejection fraction

Abstract Background Insulin resistance (IR) is a characteristic feature of heart failure (HF), and it is present both in diabetic- and non-diabetic patients with HF. It is observed in patients with HF with preserved ejection fraction (HFpEF) as well as in those with HF with reduced ejection fraction (HFrEF). It is still not fully understood how IR can affect the clinical outcome in patients with HFpEF. Triglyceride glucose index (TyG index) is a novel, simple marker of IR which is well correlated with HOMA-IR. Purpose To investigate the correlation between TyG index and clinical outcome in patients with hospitalized HFpEF. Methods We enrolled 1231 patients registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, which is a multicenter registration of patients hospitalized for acute decompensated HFpEF, for the present study. TyG index was calculated as Ln(serum triglyceride [mg/dL] x fasting blood glucose [mg/dL]/2) using blood sample before discharge. We followed the study patients for median of 387 days (IQR 239-727 days) to observe all-cause death and the major adverse cardiovascular events (MACE; composite of death, heart failure hospitalization and stroke). Results We could calculate TyG index in 917 patients (81±9 year old, 55.3% female) with the mean value of 8.5±1.5. Diabetes was observed in 360 (39.3%) patients, and they had higher TyG index than non-diabetic patients (8.8±0.6 vs. 8.4±.05, p&amp;lt;0.0001). Cox proportional hazard model selected TyG index score as an independent predictor for all-cause death regardless of history of diabetes, hypertension and dyslipidemia (p=0.004). We divided patients into 4 groups based on TyG index. Kaplan-Meier curves indicated the difference in all-cause mortality among 4 groups (Figure Left, p=0.0003 by log-rank test). Incidence of MACE was also significantly different among 4 groups (Figure Right, p=0.007 by log-rank test). Conclusion TyG index predicted all-cause mortality and MACE in patients with HFpEF regardless of diabetic state.Kaplan-Meier curves for death and MACE

Validation of the GRACE 3.0 score and redefinition of the risk threshold for early invasive treatment in non-ST-segment elevation acute coronary syndromes: a modelling study from five countries

Abstract Background Clinical use of the GRACE scoring system is recommended across international guidelines to guide early treatment stratification in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Recently, the machine learning-based GRACE 3.0 score was derived from patients with NSTE-ACS undergoing contemporary treatment approaches. External validation studies and the reassessment of clinical risk categories are lacking. Purpose We aimed to evaluate the predictive performance of the GRACE 3.0 score and to explore clinically meaningful risk groups in contemporary patients with NSTE-ACS. Methods We studied the GRACE 3.0 score in 8070 patients with NSTE-ACS in contemporary ACS cohorts from Denmark (VERDICT, n=2147), Germany (Heidelberg-ACS, n=2034), Italy and Spain (CORALYS, n=1650), and Switzerland (SPUM-ACS, n=2239). Heterogeneity in the treatment effect of very early invasive management (within 12 hours) or standard invasive management (within 48 to 72 hours) on the primary composite outcome of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure in relation to baseline mortality risk was assessed in 2147 patients enrolled in the VERDICT trial who were randomized to different timing of invasive treatment. Results The GRACE 3.0 score showed excellent discriminatory properties with an area under the receiver operating characteristic curve (AUC) for in-hospital death of 0.89 (95% CI, 0.85–0.93) in the total study cohort. Similar results were observed in Denmark (AUC 0.93, 95% CI, 0.88–0.98), Germany (AUC 0.90, 95% CI, 0.85–0.94), and Italy and Spain (AUC 0.85, 95% CI, 0.77–0.94), and Switzerland (AUC 0.93, 95% CI, 0.86–1.00). Early invasive treatment reduced the composite endpoint (absolute risk reduction: 0.12, 95% CI, 0.03–0.21, P=0.011) in patients at high risk (≥1.7%), but not in those with lower risk profiles (P interaction=0.033). Based on this new high-risk threshold, GRACE 3.0 stratified 475 (42.2%) more patients into the high-risk group, as compared to traditional GRACE risk categories (P&amp;lt;0.001). Conclusion GRACE 3.0 shows unprecedented predictive performance in patients with NSTE-ACS. In the context of a comprehensive clinical evaluation, GRACE 3.0 can support clinical decision making for the timing of invasive treatment. The high-risk group of patients with NSTE-ACS who benefit from early invasive treatment is substantially larger than previously described.ROC curve and risk groupsRestratfication towards high risk group

Does discontinuing bleomycin due to toxicity increase the risk of lymphoma progression? Real-life data from a homogeneous population of advanced stage Hodgkin lymphoma

Hodgkin Lymphoma (HL) is often curable with ABVD therapy and improving outcomes is a main goal of ongoing research. Bleomycin-associated pneumonitis (BAPT) is a potentially life-threatening complication that necessitates bleomycin discontinuation. We conducted this study on a homogenous cohort of advanced stage HL treated only with ABVD for frontline therapy to assess if bleomycin discontinuation increases the risk of lymphoma progression. After the exclusion of patients who received radiotherapy or other drugs, 106 and 28 patients in the six-cycle ABVD and BAPT groups respectively had similar survival curves for progression and death with a 49-month median follow-up. PFS rates were also very similar at two and four years from diagnosis with 2-year PFS rates of 83.9% and 82.1% (RR = 1.1 95%CI = 0.45–2.2). Outcome comparisons were also similar between the two groups when stratified according to early response assessment with PET/CT. Patients who discontinued bleomycin due to toxicity did not experience an increased risk of progression compared to patients who completed six ABVD cycles.

Long-term effectiveness and safety of edoxaban in patients with atrial fibrillation: 4-year follow-up of more than 13,000 patients from the ETNA-AF-Europe study

Abstract Background Direct, non-vitamin K antagonist oral anticoagulants (DOACs/NOACs) have become the first-choice therapy for stroke prevention in patients with atrial fibrillation (AF) at risk of stroke. Data on long-term effectiveness and safety of NOACs are scarce and not available from randomised clinical trials. Purpose We analysed 4-year outcome data in 13,632 European patients with AF treated with the NOAC, edoxaban. Methods This is the first report of the four-year follow-up information collected in the ETNA-AF-Europe (NCT02944019) study. It is a prospective registry, conducted in 825 centres enrolling edoxaban-treated patients in 10 European countries. Design and follow-up were agreed with the European Medicines Agency as part of the post-approval safety assessment of edoxaban. Key efficacy and safety outcomes were adjudicated. Results 13,164 patients (56.7% males) with AF treated with edoxaban (60 mg OD n=9617; 30 mg OD n=3042; missing dose n=505) were analysed: median (interquartile range [IQR]) age was 75 (68–80) years, weight 80 (70–90) kg, creatinine clearance (CrCl) 68.9 (52.7–87.9) mL/min, modified CHA2DS2-VASc and HAS-BLED scores 3 (2–4) and 2 (1–2), respectively in the overall population. Annualised all-cause and cardiovascular deaths in the overall population were 4.1%/year and 1.0%/year, respectively; higher in the edoxaban 30 mg vs 60 mg cohort (Figure 1). Annualised rates of stroke, transient ischaemic attack and systemic embolic events rates were &amp;lt;1% (0.6%/year, 0.3%/year and 0.1%/year, respectively); these proportions were similar between the two dose cohorts (Figure 1). The time-to-first event curves for all-cause death, stroke and major bleeding were almost linear throughout the 4-year follow-up (Figure 2), irrespective of dose cohort. Compared with patients receiving edoxaban 60 mg, those prescribed 30 mg were older (median [IQR] age: 80 [75–85] vs 73 [66–78] years), had greater frail proportion (27.0% vs 6.6%), a lower CrCl (46.1 [37.4–59.0] vs 75.9 [61.9–93.8] mL/min) and a higher CHA2DS2-VASc score (4 [3–5] vs 3 [2–4]). Annualised bleeding rate was 3.0%/year and higher in the 30 mg vs 60 mg cohort (Figure 1). Annualised major bleeding, intracranial haemorrhage (ICH) and major gastrointestinal (GI) bleeding rates were low (0.9%/year, 0.2%/year and 0.4%/year, respectively), with higher major bleeding and major GI bleeding rates in patients treated with edoxaban 30 mg OD (Figure 1). ICH rates were similar in both dose cohorts. Conclusion These findings illustrate the long-term effectiveness and safety of edoxaban. Treatment with edoxaban over 4 years in patients with AF is associated with a relatively low, linearly increasing rate of all-cause death and ischaemic stroke. Rates of bleeding and especially ICH rates were low.

The relationship between diabetes, obesity and cardiovascular disease phenotypes: a UK Biobank cohort study

Abstract Background Obesity and diabetes mellitus (DM) frequently co-exist, yet their individual contributions to cardiovascular risk remain debated. Purpose We explored cardiovascular disease biomarkers, events and mortality in a large cohort stratified by body mass index (BMI) and DM. We hypothesised that DM with normal BMI is associated with a cardiovascular phenotype and event rate comparable to obesity without DM. Methods 451,355 UK Biobank participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and DM status. We examined cardiovascular biomarkers including: carotid intima-media thickness (CIMT); arterial stiffness; left ventricular ejection fraction (LVEF) and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRR) for myocardial infarction, ischaemic stroke and cardiovascular death, with normal weight non-DM as comparator. Correlation matrices of Poisson model’s coefficients were used to assess correlations between covariates. Results 5% of participants had DM (10% normal weight, 34% overweight and 55% obese; versus 34%, 43% and 23%, respectively, in non-DM). In the non-DM group, overweight/obesity was associated with higher CIMT, arterial stiffness and CCI, and lower LVEF (p&amp;lt;0.05); these relationships were diminished in the DM group. Within BMI classes, DM was associated with adverse cardiovascular phenotype (p&amp;lt;0.05), particularly in the normal weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischaemic stroke and cardiovascular mortality all rose across increasing BMI categories in the DM and non-DM groups (p&amp;lt;0.05). However, normal weight DM had higher cardiovascular mortality than obese non-DM (IRR 2.81 [95% confidence interval: 2.24-3.54] vs IRR 1.84 [1.70-1.98]). Pairwise correlation analysis demonstrated the strongest correlates of cardiovascular parameters were markers of adiposity; this was apparent in the DM and non-DM groups, although these remained modest with Pearson’s correlation coefficients of no more than 0.25. Conclusions Obesity and DM are additively associated with adverse cardiovascular biomarkers and mortality risk. Whilst adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting other factors underpin the high cardiovascular risk of normal-weight diabetes. Ideal target range for metrics of adiposity may therefore be lower than currently proposed in people with DM.Table 1:Adjusted IRR of CV deathFigure 1:KM Curve for CV death

Risk stratification of hemodynamically stable patients with acute pulmonary embolism: external validation and comparison of different strategies

Abstract Background Risk stratification for adverse outcome in hemodynamically stable patients with acute pulmonary embolism (PE) remains an issue. We aimed at validating and comparing currently available tools for risk stratification in this setting. Methods Hemodynamically stable patients (n= 5,036) from a prospective, multicentre study of adult patients with acute, symptomatic, objectively diagnosed PE (COPE) were included in this study. Study outcomes were in-hospital death, death at 30 days, PE-related death and the composite of clinical deterioration or death at 30 days. We assessed and compared the accuracy of ESC-2014, ESC-2019, PEITHO, Bova, TELOS, FAST and NEWS2 models to predict study outcome events by AUC statistics, negative and positive predictive values. Results Patient distribution in risk categories highly varied across different models (low-risk class: from 14.4% in ESC-2019 to 70.1% in FAST; highest risk class: from 16.4% in BOVA to 43.7% in ESC 2014). When the 3,544 patients with echocardiography performed and troponin assessed were considered, ESC-2014, PEITHO, TELOS and NEWS-2 had i) the best discriminatory powers for study outcome events, ii) the best performances for all study outcome events (ROC curves for death or clinical deterioration reported in the Figure) and iii) negative predictive values for PE-related death above 99%. Negative predictive values for death or clinical deterioration were above 98% for all the models except for FAST; positive predictive values were all below 10% except for TELOS. TELOS score had the best performance; NEWS2 score was very good by including clinical variables only (no instrumental/laboratory items). Conclusions The majority of available models for risk stratification of patients with acute PE have good accuracy for the identification of low-risk patients; their positive predictive values in hemodynamically stable patients remain modest, the best being that of TELOS score. These data are essential to inform management studies.

An International Validation of the "DECAF Score" to Predict Disease Severity and Hospital Mortality in Acute Exacerbation of COPD in the UAE.

The DECAF score (the Dyspnea, Eosinopenia, Consolidation, Academia, and Atrial fibrillation score) has been adopted in some hospitals to predict the severity of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD). However, DECAF score has not been widely evaluated or used in Middle Eastern countries. The present study aimed to validate the DECAF score for predicting in-hospital mortality in patients with AECOPD in the United Arab Emirates (UAE). This was a retrospective, observational study conducted in 19 hospitals in the UAE. Data were retrieved from the electronic records of patients admitted for AECOPD in 17 hospitals across the country. Patients aged more than 35 years who were diagnosed with AECOPD were included in the study. The validation of the DECAF Score for inpatient death, 30-days death, and 90-day readmission was conducted using the Area Under the Receiver Operator curve (AUROC). The AUROCDECAF curves for inpatient death, 30-days death, and 90-day readmission were 0.8 (95% CI: 0.8-0.9), 0.8 (95% CI: 0.7-0.8), and 0.8 (95% CI: 0.8-0.8), respectively. The model was a satisfactory fit to the data (Hosmer-Lemeshow statistic = 0.195, Nagelkerke R2 = 31.7%). There were significant differences in means of length of stay across patients with different DECAF score (P = .008). Patients with a DECAF score of 6 had the highest mean length of stay, which was 29.8 ± 31.4 days. Patients with a DECAF score of 0 had the lowest mean length of stay, which was 3.6 ± 2.0 days. The DECAF score is a strong predictive tool for inpatient death, 30 days mortality and 90-day readmission in UAE hospital settings. The DECAF score is an effective tool for predicating mortality and other disease outcomes in patients with AECOPD in the UAE; hence, clinicians would be more empowered to make appropriate clinical decisions by using the DECAF score.