Mortality Curves Research Articles

Impact of QRS complex fragmentation on all-cause mortality before and after cardiac resynchronization therapy

Abstract Introduction Cardiac resynchronization therapy (CRT) have demonstrated to reduce all-cause mortality in selected patients with HFrEF. However, there is still a high rate of non-responders, so risk stratification is crucial. Fragmentation of the QRS complex (QRSf) has been suggested as a valuable prognostic factor in different cardiac diseases, but the evidence in patients undergoing CRT is controversial and limited. Purpose To evaluate if changes in QRSf status before and after CRT implantation has a prognostic role in patients undergoing CRT in terms all-cause mortality. Methods Consecutive patients undergoing CRT were prospectively included from October 2009 to December 2022. Demographic clinical, electrocardiographic and echocardiographic variables were recorded. Prospective follow-up variables were collected from electronic clinical records and telephone interview. QRSf complex was defined by the presence of different RSR′ patterns including additional R-waves (R′) and notches of the R-wave and S-wave in two contiguous leads corresponding to a main coronary artery territory in a 12-lead electrocardiogram performed before and after CRT. Results A total of 244 patients (mean age 71.8 ± 9.8 years, 79.5% male) were included. The etiology of LV systolic disfunction was ischemic in 50.0%. Mean LVEF before implantation was 25 ± 9%. A CRT-D was implanted in 176 patients (72.2%). The mean width of the paced QRS was 141 ± 23 ms. At baseline, 150 patients had a QRSf. After CRT implantation, 69 (28.4%) patients experimented a change in QRSf status: 29 patients (11.9%) without prior QRSf developed QRSf, whereas 40 patients (16.5%) resolved QRSf after CRT. Median follow-up time was 36.0 months (interquartile range 18.2-75.7). During the follow-up period, 90 patients died. In the multivariate Cox regression survival analysis, the presence of QRSf before the implantation with or without paced QRSf after CRT were independently associated with all-cause mortality (HR 4.43; 95% CI 1.53-12.80 and HR 3.69; 95% CI 1.16-11.80 respectively). Those without QRSf prior implantation who developed QRSf after CRT did not present significantly higher risk of all-cause mortality. Univariate and multivariate Cox regression analyses for all-cause mortality are presented in Table 1. Figure 1 presents Kaplan-Meier curves for all-cause mortality according to QRSf status before and after CRT implantation. Conclusions According to our results, preimplantation QRSf is an independent predictor of all-cause mortality regardless the resolution or maintenance of QRSf after CRT in patients with HFrEF undergoing CRT. Therefore, patients with QRSf before CRT implantation regardless the paced QRSf status, should be followed more strictly because they are at higher mortality risk.Table 1.Cox Regression Analyses

Age-based comparison of patients with heart failure treated with sacubitril-valsartan in France: a real-world evaluation

Abstract Background Sacubitril-Valsartan (S/V) was approved in Europe in 2015, for treatment of adults with symptomatic chronic heart failure with reduced left ventricular ejection fraction (HFrEF). In France, S/V had benefited from an early access program (2015-2018) and became available in community pharmacy since October 2018. Purpose Our study aimed to describe characteristics of patients who received S/V in France and to assess real-life mortality in this population regarding age. Methods This non-interventional retrospective study utilized existing claims data from the French National Healthcare Data System (SNDS) allowing long-term follow-up of patients who benefited from at least one reimbursement of S/V. Patient data between April 2012 and December 2020 were extracted from the database. Prespecified subgroup analyses were conducted for subjects aged <75 and ≥75 y to describe characteristics of patients at first reimbursement of S/V. Cardiovascular mortality and all-cause mortality were estimated using Kaplan-Meier method. Results Between 2015 and 2020, 104,910 patients initiated S/V and were followed for an average of 20 months; 42.6% (44,743 patients) were ≥75 y. Mean (SD) age difference between the 2 subgroups was 20.3 years [62.2 (9.6) vs 82.5 (5.2) in patients <75 and ≥75 y respectively]. Patients ≥75 y had a higher prevalence of atrial fibrillation (50.6% vs 31.2%) and chronic renal failure (20.9% vs 10.1%) and were less co-treated with mineralocorticoid-receptor antagonists (21.8% vs 40.5%) and ß-Blockers (64.0% vs 73.8%) compared to those <75 y. Three months after first dispensation, 48.3%, 35.3%, and 16.4% of patients aged ≥75 y received S/V dosages of 24/26mg, 49/51mg, and 97/103mg respectively, compared to 31.4%, 38.2%, and 30.4% for patients aged <75 y. The mean (SD) exposure period was 14.7 (13.6) months in patients ≥75 y vs 19.0 (15.5) months in <75 y patients. As expected, given the age difference, patients ≥75 y had a higher probability of all-cause mortality at 12-month 16.5% vs 6.2% in patients <75 y. Furthermore, 12-month cardiovascular mortality – evaluated during the early access program period (2015-2017) – in patients ≥75 y was 11.0% vs 4.8% in patients <75 y. Figures 1 and 2 show survival curves for cardiovascular mortality and all-cause mortality of these 2 subgroups. Of interest, cardiovascular mortality rate at 12 months was 7% in this study, compared to 6% in PARADIGM-HF, and all-cause mortality at 12-month was higher (10,6% vs 7%), likely due to the profile of the patients, who were older and have more comorbidities in real life. Finally, very few patients were hospitalized for reasons related to angioedema, 16/44,743 in ≥75 y patients and 26/60,167 in those <75 y. Conclusion This is the first French real-world study providing exhaustive nationwide data on S/V mortality over a period of almost 6 years in a very large population of elderly with a mean age of 70.9 y vs 63.8 y in PARADIGM-HF.Figure 1Figure 2

Contemporary characteristics, outcomes and novel risk score for Takotsubo cardiomyopathy: a national inpatient sample analysis

Abstract Background Takotsubo cardiomyopathy (TC) is an established differential diagnosis in the category of myocardial infarction with non-obstructive coronaries with significant recent interest but limited data on prognostication. We reviewed the characteristics and in-hospital outcomes and developed a novel risk score for TC. Methods Adult patients (≥18 years of age) with a diagnosis of acute coronary syndrome (ACS) and TC were identified from the National Inpatient Sample 2016-2020 in the United States. The cohort was divided into ACS with and without TC, and the related baseline data was retrieved. Multivariable regression analysis was performed to identify clinical factors associated with TC and its adverse outcomes and to create a risk-scoring system estimating mortality risk in the TC cohort. Results Amongst 7,219,004 adult patients admitted for ACS, 78,214 (1.0%) were diagnosed with TC, with a mean age of 68.2 years, 64,526 (82.5%) being female, and 5,475 (7.0%, compared with 8.4% for other ACS) in-hospital mortality events. Key factors significantly associated with TC diagnosis were female sex (OR 6.78 (95%CI 6.47-7.09), p<0.001) and chronic heart failure (OR 1.60 (95%CI 1.54-1.66), p<0.001). Based on multivariable analyses for in-hospital mortality in TC patients, a novel risk score was developed, with parameters and score assignment listed in the Figure. The score can be divided into three categories: low risk (-3 to +3), moderate risk (4 to 7), and high risk (8 to 19), and its area under curves for in-hospital mortality were 0.716 in the derivation and 0.726 in the validation cohorts. Conclusion TC remains a high-risk diagnosis in a minority of ACS hospitalizations, with comparable in-hospital mortality rates to other causes of ACS. A novel score was developed to risk stratify TC inpatients with moderate discrimination and internal validation, warranting external validation.Takotsubo Cardiomyopathy Risk Score

Obesity paradox exists in super elderly patients with heart failure

Abstract Background Aging and obesity are two global concerns in public health. As obesity is associated with several metabolic disorders, it is a well-known risk factor of heart failure (HF). However, several studies have suggested that obesity may have paradoxical survival benefits in patients with HF. Therefore, the aim of this study was to investigate whether the obesity paradox exists in super elderly patients with HF in Japan. Methods A total of 4,292 patients from our hospital HF registry were divided into four age subgroups: (A) less than 65, (B) elderly 65-74, (C) high elderly 75-84, (D) super elderly ≥85. The primary endpoint was the all-cause death within 1-year after discharge. Results At baseline, the proportion of men in each group was 42-76%, the mean left ventricular ejection fraction was 49-61%, the average of N-terminal pro-B-type natriuretic peptide was 1972-2944 pg/ml, and the mean body mass index (BMI) ranged 21-25 kg/m2. Patients with higher BMI were more common in the younger age group, while those with lower BMI were more common in the older age group. Cubic spline curves of Cox proportional hazard regression models demonstrated an inverse relationship between BMI and mortality (Fig. 1). Lower BMI was associated with higher all-cause mortality in all ages, although this association was attenuated at the young age, and pre-obesity (25–29.9 kg/m2) was associated with the greatest survival benefit. Meanwhile, the impact of underweight (<18.5 kg/m2) was stronger super elderly subjects, a one-unit increase in BMI was associated with a 10.3% decrease in the hazard ratio of death (P=0.021). Kaplan-Meier curves for all-cause mortality also showed that lower BMI was associated with higher all-cause mortality in all groups, and the differences were statistically significant in Groups B, C, and D (Fig. 2). Conclusion Our study suggested the existence of the obesity paradox among HF patients in super elderly. Mildly overweight may be beneficial at old age with HF.

Ticagrelor or prasugrel versus clopidogrel in patients with coronary heart disease

Abstract Introduction Antiplatelet therapy is pivotal in the management of coronary heart disease (CHD), especially after percutaneous coronary intervention (PCI). Clopidogrel has long been the cornerstone of dual antiplatelet therapy. However, newer agents like prasugrel and ticagrelor boast of faster onset of action and greater platelet inhibition, which may translate to improved outcomes. Purpose Our hypothesis is that prasugrel or ticagrelor are superior to clopidogrel in reducing cardiovascular mortality in chronic CHD patients. Methods We conducted a retrospective cohort study using the TriNetX network database, including patients with chronic CHD on dual antiplatelet therapy. A total of 1,420,165 patients on clopidogrel and 197,783 on prasugrel or ticagrelor were identified. We assessed the primary composite endpoint of cardiovascular mortality over a 5-year follow-up period, using event-free survival as our main outcome measure. Results The 5-year follow-up data revealed a significant difference in event-free survival between the groups. Patients on prasugrel or ticagrelor had a markedly higher event-free survival rate of 83.156% compared to 73.209% for those on clopidogrel. The Log Rank test showed a confidence interval of 1.544 to 1.592 with a highly significant p-value of <0.0001. Discussion The data suggest a clear benefit of prasugrel or ticagrelor over clopidogrel for event-free survival in CHD patients. This could be attributed to the more potent antiplatelet effects of these drugs, leading to reduced thrombotic events. Given the substantial sample size and robustness of the data, the findings advocate for a paradigm shift in the choice of more potent antiplatelet agents in clinical practice. Conclusion Our analysis supports the hypothesis that prasugrel or ticagrelor are associated with significantly lower cardiovascular mortality compared to clopidogrel in patients with chronic coronary heart disease.5-year Kaplan-Meier curves for mortality

Association of Sleep Apnea and cardiovascular mortality in CAD patients

Abstract Background A growing body of epidemiological and clinical research has uncovered a significant relationship between sleep apnea and the exacerbation of cardiovascular outcomes, notably myocardial infarction, stroke, and cardiac death. Individuals diagnosed with coronary artery disease (CAD) alongside sleep apnea are identified to have a heightened likelihood of experiencing recurrent cardiovascular events. Despite these associations, the link between sleep apnea and an elevated risk of mortality among CAD patients remains insufficiently explored. Purpose Our study aims to shed light on the impact of sleep apnea on mortality rates within this patient population, potentially guiding future therapeutic strategies. Methods Our cohort study leveraged data from the TriNetX multinational electronic health record network, focusing on patients aged 18 and above diagnosed with coronary artery disease. Participants were stratified into two groups based on the diagnosis of sleep apnea. To ensure a fair comparison, we adjusted for prevalent risk factors such as hypertension, diabetes, dyslipidemia, obesity, and chronic kidney disease, which are commonly observed in CAD patients. Results The study encompassed 1,799,812 patients, equally divided into two groups of 899,906 individuals each, one with sleep apnea and the other without. Over a 5-year observation period, the primary endpoint, defined as event-free survival, was significantly lower in the sleep apnea group (74.385%) compared to the non-sleep apnea group (76.606%), with a Log Rank confidence interval of 1.128 to 1.148 and a p-value of <0.0001. This outcome highlights a association between sleep apnea and increased mortality rates in CAD patients. Conclusion The findings from our large cohort study underscore the critical impact of sleep apnea on mortality among patients with coronary artery disease. The diagnosis of sleep apnea in CAD patients within the TriNetX cohort was significantly associated with a higher mortality rate over a span of five years. These insights emphasize the need for integrated care strategies that not only address the primary cardiovascular conditions but also prioritize the diagnosis and management of sleep apnea to potentially improve survival outcomes in this vulnerable patient group. Our study calls for heightened clinical awareness and further research to elucidate the mechanisms behind this association and to explore the benefits of targeted sleep apnea interventions in reducing mortality rates among CAD patients.5-year Kaplan-Meier curves for mortality

Evolution and prognostic relevance of right ventricular morphofunctional parameters in patients undergoing isolated tricuspid valve surgery

Abstract Background Right ventricular (RV) function is key in evolution after isolated tricuspid valve surgery (ITVS). Right ventricular-pulmonary artery coupling (RV-PA coupling), determined with echocardiography as the ratio TAPSE/sPAP, has merged as a relevant functional parameter in many clinical scenarios. Purpose Our aim is to evaluate the prognostic relevance of RV-PA coupling in patients undergoing ITVS. Methods We carried out a retrospective study involving all the patients undergoing ITVS at our tertiary centre. Several RV function measurements were assessed from the baseline echocardiogram (TAPSE, fractional area change (FAC), systolic pulmonary artery pressure (sPAP), tricuspid annulus tissue Doppler velocity (RVS´) and free-wall global longitudinal strain (FW-GLS)) and RV-PA coupling was calculated. Association between RV morphofunctional variables and mortality during one year follow-up was determined. Results 45 patients were included (68 years-old, 51,1% female). The most common TR etiology was functional (51.1%) and 42.2% had previous left-sided valvular surgery. The median Tri-Score was 2 (1-4) points and the most frequent procedure was biological valve replacement (65%). Baseline echocardiographic parameters were as follows: basal 52 (48 – 53.5) mm, mid 40 (36-45.5) mm and longitudinal 73 (68-80) RV diameters, TAPSE 18.1 (15.5-20.7) mm, RVS´ 10.1 (9-12.5) cm/s, FAC 0.5 (0.43-0.57), sPAP 35 (31.5-37.5) mmHg, and FW-GLS - 21.1 (17.2-25) %. During the follow-up 8 (18%) patients died. Solely TAPSE (16 vs 19, p= 0.047) and RV-PA coupling (0.35 vs 0.5; p= 0.035) showed significant differences in mortality among RV echocardiographic parameters. An RV-PA coupling <0.375 mm/mmHg appeared to be the best mortality predictor (RR 1.45; p= 0.04) one year after the intervention (Figure). Conclusions In our series RV-PA coupling has proved to be the best echocardiographic prognostic factor in ITVS, so it could be considered a relevant parameter in risk stratification previous to this surgery. Figure. Kaplan Meier curves of mortality after ITVS by RV-PA coupling.Figure

Changing patterns in clinical, echocardiographic and haemodynamic characteristics, and management strategies that may be translated to improved survival in pulmonary hypertension

Abstract Background and aims In this retrospective analysis of a single-center series on pulmonary hypertension (PH), we aimed to evaluate clinical, echocardiographic, and hemodynamic characteristics, management strategies, morbidity, and mortality in PH subgroups across three consecutive periods. Methods The study included 1071 patients enrolled in the Evaluation of Pulmonary Hypertension Risk factors Associated with Survival study (EUPHRATES). In reference to enrollment time, patients were assessed in three periods ; before 2016, the era of primarily monotherapy or sequential combinations; between 2016 and 2019, post-approval and reimbursement of macitentan in our country, marking a shift towards more proactive sequential combinations; and after 2019, signifying the initiation of earlier sequential combinations with selexipag in pulmonary arterial hypertension (PAH). The ESC/ERS 2022 risk scoring, COMPERA 2.0 and REVEAL lite 2 models were used for risk predictions. Composite endpoint (CEP) definitions were adopted from the SERAPHIN and GRIPHON trials. Annual incidence curves for mortality and CEP were evaluated, but 2020 analysis was adjusted to account for the possible adverse effects of the COVID-19. Results During the 1st, 2nd and 3rd periods, 481, 352, and 238 patients with PH were diagnosed, respectively. Incident cases comprised 91% of them. Idiopathic PAH (IPAH), PAH-associated with congenital heart diseases (CHD-PAH), PAH-associated with connective tissue diseases (CTD-PAH), group II, III, IV and V PH were documented in 24 %, 28 %, 4.6 %, 4.3 %, 11%, 27 % and 0.7 % of patients, respectively. Age and female dominance remained unchanged. Incidences of Group 1 PH and CHD-PAH decreased while IPAH, drug-associated PAH, and Group II and IV PH increased across three periods (p-values varying from <0.001 to 0.03). Although baseline functional class became worse (p=0.013), six-minute walk distance, N-terminal pro brain natriuretic peptide and risk scores showed no change (p=NS). Baseline echo and hemodynamic measures became better, and triple combinations increased after 2019 (p<0.001 for all). For overall PH, rates of all-cause mortality and CEPs at 1st, 2nd and 3rd periods were 52 % and 59 %, 30 % and 35 %, and 11 % and 13 %, respectively (p< 0.001, for all). Mortality rates for 1st, 2nd and 3rd periods were 36 %, 38 % and 26 % in IPAH, 60 %, 28 % and 13 % in CHD-PAH, 55 %, 22% and 22% in CTD-PAH, 38 %, 38% and 24 % in group IV PH, respectively (p< 0.001, for all). Mortality curves showed sudden increases in 2020, but excluding 2020, a steady improvement in the annual mortality was evident. Conclusions Our findings suggest a trend towards better clinical, echocardiographic, and hemodynamic presentations and improved survival in the PAH subgroups, and Group IV PH across the three periods that might be attributed to more proactive management strategies favouring earlier initiation of combinations.

Validation of the MIDA mortality risk score in a surgical cohort of patients with primary mitral regurgitation

Abstract Background and aim The MIDA scale is a prognostic tool for stratification of short- and long-term mortality risk in patients with primary mitral regurgitation (PMR). The aim of this study is to validate the MIDA (1) score in our population of PMR treated with surgery. Methods Retrospective analysis of a prospective cohort of patients with PMR who underwent mitral valve surgery in a tertiary care center from 2014 to 2022. The necessary parameters for calculating the MIDA Score (age, symptoms, atrial fibrillation, left atrial diameter, right ventricular systolic pressure (RVSP), left ventricular end-systolic diameter (LVESD), and LV ejection fraction (LVEF)) were collected, and the MIDA score for each patient was calculated. Thereafter, patients were classified into seven different risk groups. One year and long-term mortality during follow-up were recorded. A logistic regression analysis was performed to evaluate the association of each parameter with outcomes. Finally, curves for the cumulative incidence of all-cause mortality according to the MIDA score were generated with the Kaplan–Meier method. Results A total of 349 patients were included. Mean age was 68.5 [12.4] years, 55.8% were male, and the median LVEF was 60% (55-65). Mean follow up was 3.28 (2) years. One year mortality occurred in 29 (8.3%) patients, and long-term mortality in 59 (16.9%). According to the MIDA score, the distribution of patients in each subgroup was as follows: score 0 (n=28), score 1-2 (n=35), score 3-4 (n=60), score 5-6 (n=99), score 7-8 (n=81), score 9-10 (n=35), score > 11 (n=11). Most of our cohort was classified as intermediate-risk patients, with a median score of 6 (3-8). In the univariable logistic regression analysis, age, symptoms before surgery and RVSP were the only MIDA parameters significantly associated with mortality (Table-Figure 1). In our population, the discriminatory capacity of the MIDA score, was moderate, with an area under the ROC curve of 0.676 CI (0.624-0.725) for one year mortality, and 0.702 (0.651-0.749) for long term mortality. The best cut-off point for predicting one-year and long-term mortality was a MIDA score of 7. Kaplan-Meier curves for mortality during follow-up are shown in Figure 2. Conclusions The MIDA score showed a fair discriminatory capacity in our surgical cohort of patients with PMR. Variables included in the score that had a significant association with mortality were age, presence of symptoms and elevated RVSP. LV parameters included in the MIDA, which are the current class I indication for surgery, did not show a significant association with outcomes. Different echocardiographic variables to evaluate cardiac damage in PMR are needed to achieve better stratification.Table-Figure 1Figure 2

Improving morbidity and mortality in patients with pulmonary hypertension: insights from a nation-wide registry

Abstract Background and aims In this retrospective analysis of a nation-wide registry on pulmonary arterial hypertension (PAH), group IV and V, we evaluated management strategies, morbidity and mortality across three consecutive time periods. Methods This study included 903 patients enrolled from 24 cardiology centers participating in the RegiStry on clInical outcoMe and sUrvival in pulmonaRy hypertension Groups (SIMURG II). Patients were divided into three enrollment periods: before 2016, the era of monotherapy or sequential combination therapies; between 2016 and 2019, post-approval and re-imbursement of macitentan in our country, marking a shift towards more proactive sequential combinations; and after 2019, signifying the initiation of earlier sequential combinations with selexipag in PAH. ESC/ERS 2022, COMPERA 2.0 and REVEAL lite 2 models were used for risk predictions. Composite endpoint (CEP) definitions were adopted from the SERAPHIN and GRIPHON trials. Results Age (mean +SD) was 51.27 + 21.37 years, and 72 % were female. Incident cases were noted in 65.9 % of patients. Idiopathic PAH (IPAH), PAH-associated with congenital heart diseases (CHD-PAH), PAH-associated with connective tissue diseases (CTD-PAH), porto-PAH, Group IV and V pulmonary hypertension (PH) were documented in 33 %, 33.5 %, 12 %, 1.6 %, 20 % and 1.7 % of patients, respectively. Background mono and dual targeted combinations, and sequential triple combinations were noted in 17 %, 57 % and 26 % of patients, respectively. Baseline low-, intermediate-, and high-risk were noted in 1.2 %, 14.1 %, and 84.7 %, respectively. Median follow-up time (day) was 867 (412-1667). Overall rates of mortality and CEP were 26 % and 39%, respectively. There were increases in the % of PAH and group IV PH, and decreases in the % of CHD-PAH across the three periods. Prevalent versus incident cases were associated signifinatly lower mortality and CEP ( p=0.028 and p=0.024, respectively). Outcomes for mortality and CEP were predicted by three risk models (p<0.0001 for all). Mortality and CEP rates were 31 % and 44 % in IPAH, 20 % and 39 % in CHD-PAH, 31 % and 43 % in CTD-PAH, and 25 % and 30 % in group IV patients, respectively. In overall PH population, rates of mortality and CEP documented at 1st, 2nd and 3rd periods were 64 % and 67 %, 29 % and 31 %, and 3.5 % and 5.1 %, respectively (p< 0.001, for all). Mortality rates for 1st, 2nd and 3rd periods were 49 %, 39 % and 11 % in IPAH, 62 %, 33 % and 5.3 % in CHD-PAH, 47 %, 45 % and 7.7 in CTD-PAH, and 37 %, 52 % and 11 % in group IV, respectively (p< 0.001, for all). However, mortality curves showed sudden increases in 2020 that might be attributed to COVID-19. Conclusions Our nation-wide data revealed improving survival in the overall PH population, PAH and Group IV PH that might be associated with risk-based earlier targeted combination strategies. However, this trend seems to be counterbalanced with COVID-19 pandemic.

Validation of serum non-invasive tests of liver fibrosis as prognostic markers of clinical outcomes in people with fatty liver disease in Australia.

The validity of non-invasive tests (NITs) of liver fibrosis for the prediction of liver and mortality outcomes in an Australian cohort is unknown. We aimed to verify the utility of available NITs to predict overall and cause-specific mortality and major adverse liver outcome (MALO). This was an analysis from the Crossroads 1 clinic sub-study of a randomly sampled adult cohort from regional Australia between 2001 and 2003. Baseline variables included demographic details, anthropometry, health and lifestyle data, and laboratory tests. Non-alcoholic fatty liver disease (NAFLD) and metabolic-(dysfunction) associated fatty liver disease (MAFLD) were defined by fatty liver index≥60 and other accepted criteria. Outcomes were defined by the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes for linked hospitalization and death registry data. Available serum-based NITs were analyzed as predictors of overall, cardiovascular disease-related, and cancer-related mortality and MALO in those with fatty liver disease (FLD). In total, 1324 and 1444 participants were included for NAFLD and MAFLD analysis (prevalence 35.4% and 40.7%, respectively). There were 298 deaths (89 cardiovascular disease-related and 98 cancer-related) and 24 MALO over a median 19.7years of follow-up time. In both forms of FLD, fibrosis-4 index, Steatosis-Associated Fibrosis Estimator score, and Forns fibrosis score consistently had the highest area under the receiver operating characteristic curve (AUROC) for overall and cause-specific mortality, with AUROC>0.70 for each outcome. However, all had poor discriminatory ability for determining MALO in each FLD. Several liver fibrosis NITs perform similarly reasonably well in predicting the risk of mortality outcomes in those with FLD but are poorly discriminatory for MALO prediction.

The association between pan-immune-inflammation value and chronic obstructive pulmonary disease: data from NHANES 1999-2018.

The pan-immune-inflammation value (PIV) is an emerging biomarker quantitatively reflecting the systemic immune-inflammatory status. The predictive value of PIV has been well-established across various clinical settings. However, its role in chronic obstructive pulmonary disease (COPD) remains unclear and necessitates further investigation. Data from NHANES 1999-2018 were filtered. Logistic regression analyses were used to assess the correlation between COPD prevalence and PIV in all participants. COX regression analyses and Kaplan-Meier survival curves were used to investigate the relationship between COPD all-cause mortality and PIV in COPD patients. Restricted cubic spline (RCS) analyses and piecewise linear regression analyses were additionally employed to explore the correlation between PIV and COPD. Subgroup analyses were performed to further clarify the effects of other covariates on the associations. Sensitivity analyses were employed to assess the robustness of the results. A total of 28,485 participants aged 40years and older were recruited for this study. After fully adjusting for covariates, higher PIV levels were independently associated with increased COPD prevalence (OR = 1.67; 95% CI: 1.39-2.01) and all-cause mortality (HR = 2.04; 95% CI: 1.41-2.95). The COPD prevalence curve exhibited an inflection point at Log10-PIV of 2.24, showing no significant correlation on the left side (OR = 0.86; 95% CI: 0.45-1.64) but a positive correlation on the right side (OR = 2.00; 95% CI: 1.57-2.55). The COPD all-cause mortality curve displayed an inflection point at Log10-PIV of 2.38, indicating a negative correlation on the left side (HR = 0.23; 95% CI: 0.12-0.44) and a positive correlation on the right side (HR = 4.12; 95% CI: 2.62-6.48). Subgroup analyses with interaction tests showed that the strength of the correlation between PIV and COPD prevalence was influenced by race, smoking status, and BMI (all p for interaction <0.05). The relationship between PIV and COPD all-cause mortality was unaffected by any covariates (all p for interaction >0.05). Elevated PIV levels are associated with increased COPD prevalence. COPD patients with either elevated or reduced PIV levels experience higher all-cause mortality. Further large-scale, longitudinal studies are required to corroborate these findings.

Paleobiology and paleoecology of the woolly rhinoceros (Coelodonta antiquitatis) in Northern and Central Europe: New insights from multi-proxy data

The woolly rhinoceros, Coelodonta antiquitatis, was an emblematic component of Pleistocene faunas in Eurasia, which went extinct around ca. 12.5 ky BP. The loss of its tundra-steppe habitat due to climatic changes is considered the main cause for its extinction, whereas human impact was limited. In this study, we investigated the paleobiology and paleoecology of C. antiquitatis during the last glacial interval (Würm/Weichselian; 130 to 11.7 kya). We explored evolutionary trends for diet, physiology, and habitat via dental wear, enamel hypoplasia, body mass, age structure, mortality curves and stable isotopes (carbon and oxygen). Our results confirmed that C. antiquitatis was a large-sized species, with body mass around 2000–2500 kg, and with C3 grazing or mixed-feeding habits. Age structure and mortality curves revealed potential sampling and/or taphonomical biases at a few localities (e.g., Brixham cave, Ofnethöhle, North Sea), and indicated several vulnerability periods (birth, weaning, cow-calf separation/maturity) also retrieved by hypoplasia analyses. We observed some spatio-temporal fluctuations of body mass (1850–2955 kg), dietary preferences (strict to variable grazing) and hypoplasia prevalence (7.41–47.06 %) of C. antiquitatis depending on the locality, but correlation to specific climatic events (stadials-interstadials) is difficult without exact datation. These variations were however limited, highlighting a rather strict climatic niche and suggesting a high vulnerability to climatic and vegetation changes.

Hyperchloremic metabolic acidosis potentially benefiting sodium bicarbonate therapy: A multi-center cohort study

BackgroundThe use of sodium bicarbonate for metabolic acidosis has been a topic of debate, primarily due to the lack of clinical efficacy evidence. This study aims to identify which types of patients with various acid-base balance parameters can benefit from sodium bicarbonate therapy. MethodsPatients diagnosed with metabolic acidosis were screened from a large multi-center critical care database to form a retrospective cohort. Mortality curves, logistic regression analysis, simulation methods, and propensity scores were used to compare data between sodium bicarbonate (SOB group) and non-treated (Non-SOB group) patients. ResultsThere was an interaction between baseline chloride, anion gap levels and sodium bicarbonate therapy on patients' in-hospital death. As chloride levels increased, the in-hospital mortality curves of the SOB group and Non-SOB group gradually converged, with the difference narrowing from approximately 20 % to 10 %, and then gradually widened with the increase of the anion gap. Furthermore, when patients had high chloride levels (≥112 mmol/L), those in the SOB group exhibited a higher incidence of hypernatremia, hypokalemia, and hypocalcemia at 24 h, and a lower incidence of hyperchloremia. Patients in SOB group also had a lower simulated mortality. Among patients treated with sodium bicarbonate, those with low chloride had more difficulty in normalizing pH compared to those with high chloride. ConclusionsThis study identified an interaction between baseline chloride and sodium bicarbonate therapy on patient survival. Hyperchloremic metabolic acidosis may potentially benefit from sodium bicarbonate therapy. Further prospective randomized controlled studies are warranted.

Contemporary characteristics, outcomes and novel risk score for Takotsubo cardiomyopathy: a national inpatient sample analysis

BackgroundTakotsubo cardiomyopathy (TC) is an established differential diagnosis of myocardial infarction with non-obstructive coronaries with significant interest but limited data on prognostication. We reviewed the characteristics and in-hospital outcomes and...

Predictive validity of the Questionnaire for Medical Checkup of Old-Old for all-cause mortality and disability incidence.

The Questionnaire for Medical Checkup of Old-Old (QMCOO) has been used nationwide in Japan as part of the health checkup for latter-stage older adults since the financial year 2020. Although the QMCOO is useful in screening for frailty, its cutoff values for predicting adverse health outcomes have rarely been assessed. Therefore, this study aimed to calculate the cutoff values for predicting all-cause mortality and disability incidence and to evaluate their predictive validity. This study included 3837 health checkup recipients aged ≥75 years residing in Higashiura Town, Aichi Prefecture, Japan. The health checkup was conducted from June 1, 2020, to January 31, 2021. Mortality and disability incidence were analyzed separately. For the latter, participants with a disability history were excluded, leaving 3040 available for analysis. During the follow-up of 11 191 and 8550 person-years, 276 died and 438 developed a disability, respectively. The areas under the receiver operating characteristic curve (95% confidence intervals) for all-cause mortality and disability incidence were 0.68 (0.65-0.71) and 0.66 (0.63-0.68), respectively, with QMCOO cutoff values at 3/4 and 2/3 points. Cox proportional hazard models adjusted for age, sex, body mass index, self-reported diseases, and frequency of alcohol consumption demonstrated the predictive validity of those cutoff values. The optimal cutoff value of the QMCOO for predicting all-cause mortality was 3/4, while the optimal cutoff value for predicting disability incidence was 2/3 among an older Japanese population. Geriatr Gerontol Int 2024; ••: ••-••.

Dynamic estimates of survival in patients with follicular thyroid cancer: a retrospective cohort study.

Few studies have been conducted on the dynamic survival rates of follicular thyroid cancer (FTC). This study aimed to ascertain how the survival probability of patients with FTC changes over time. In this retrospective analysis, 10,617 patients diagnosed with FTC between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database were included. Actuarial disease-specific survival (DSS) was estimated using the Kaplan-Meier method, and the log-rank test was used for comparisons. The annual hazard of mortality was determined using the hazard function, and the conditional survival (CS) was calculated using the life table method. A total of 459 (4.3%) patients died of FTC, and the 5-year and 10-year DSS rates were 96.6 ± 0.2% and 94.6 ± 0.3%, respectively. There was a statistically significant difference in the DSS rate between patients with different SEER combined summary stages (P < 0.001). The annual hazard curve for cancer mortality in the entire study cohort displayed a steep downward trend with a slight peak at 2.5 years after diagnosis, followed by a gradual decline. Patients with distant metastases exhibited a higher mortality hazard curve and more notable declining trend. CS demonstrated an upward trend across the entire study population, with the most pronounced trend in patients with distant metastases. Prognosis improved over time in a stage-dependent manner in patients with FTC after diagnosis. The most significant improvement was observed in the patients with distant metastases. Notably, dynamic survival estimations, such as death hazard and conditional survival analysis, provide more precise survival projections than traditional survival analysis for FTC survivors.

Association of urinary albumin excretion with all-cause and cardiovascular mortality among patients with rheumatoid arthritis: a national prospective study.

Rheumatoid arthritis (RA) patients suffering from chronic renal insufficiency tend to exhibit subtle manifestations at the beginning. Urine albumin to creatinine ratio (ACR) is a sensitive indicator for early assessment of renal function. However, it is unclear whether it serves as an independent risk factor influencing the prognosis of RA patients. National Health and Nutrition Examination Survey (NHANES) data from 2009-2018 were included. Kaplan-Meier (K-M) curves were plotted to compare the cumulative survival probability of RA patients with different urinary albumin excretion. The association of ACR with mortality among RA patients was investigated with Cox regression model, restricted cubic spline (RCS) and stratified analyses. The prognostic efficacy of ACR and estimated glomerular filtration rate (eGFR) was evaluated by receiver operating characteristic (ROC) curves. The Cox regression model adjusted with covariates showed a 53% (HR 1.53, 95% CI 1.06-2.21) increase in all-cause mortality and a statistically non-significant increase in cardiovascular disease (CVD) mortality in RA patients with microalbuminuria (30mg/g ≤ACR<300mg/g). ACR≥300mg/g was associated with an increase in all-cause mortality (HR 2.62, 95% CI 1.55-4.45) and CVD mortality (HR 5.67, 95% CI 1.96-16.39). RCS demonstrated a nonlinear correlation between ACR and all-cause mortality in RA patients with microalbuminuria. Subgroup analysis showed that CVD mortality was higher in RA patients with microalbuminuria characterized by the following features: female, other ethnicity, eGFR≥60 ml/min/1.73 m2, hypertension or hyperlipidemia. Compared with eGFR, ACR provided better prognostic efficacy than eGFR with higher values of the area under the curve (AUC) for all-cause mortality (AUC=0.683, 95% CI 0.613-0.754) and CVD mortality (AUC=0.681, 95% CI 0.541-0.820). ACR is an independent risk factor affecting the prognosis of RA patients. The all-cause mortality was increased in RA patients with albuminuria. There was an upward trend in the CVD mortality of those with macroalbuminuria when ACR increased.

Soluble urokinase type plasminogen activator receptor (suPAR) and mortality in acute pulmonary embolism

IntroductionThe soluble urokinase-type plasminogen activator receptor (suPAR) potentially plays a role in immune-thrombosis, possibly by modulating plasmin activity or contributing to chemotaxis in a complex, poorly understood context. The role of suPAR levels in the short-term prognostic of patients with pulmonary embolism (PE) has not been evaluated. Material and methodsThis observational, prospective, single-center study enrolled consecutive patients aged 18 and above with confirmed acute symptomatic PE and no prior anticoagulant therapy. The primary objective was to assess the prognostic capacity of suPAR levels measured at the time of diagnosis in terms of mortality. ResultsFifty-two patients, with a mean age of 73.8 years (±17), were included, with gender distribution evenly split at 50%. Seven (13.5%) patients died. The ROC curve for mortality yielded an AUC of 0.72 (95% CI 0.48–0.96), with an optimal suPAR cut-off of 5.5ng/mL. Bivariate analysis for suPAR>5.5ng/mL was associated with a crude odds ratio of 10 (95% CI 1.63–61.27; p=0.01) for 30-day mortality. Survival analysis showed a 30-day mortality hazard ratio of 8.33 (95% CI 1.69–40.99; p<0.01). ConclusionsuPAR emerges as a potential biomarker for short-term mortality prediction and holds the potential for enhanced stratification in patients with acute symptomatic PE.

Toxicity and Sublethal Effects of Piper hispidinervum Essential Oil on Behavioral and Physiological Responses of Sitophilus zeamais Populations.

This study aimed to evaluate the toxicity of Piper hispidinervum essential oil (PHEO) against 11 Brazilian populations of Sitophilus zeamais (Coleoptera: Curculionidae). The effects of sublethal doses of PHEO on the behavior (walking and flying), respiration, and population growth (ri) of the insect populations were investigated. PHEO toxicity was determined through concentration-mortality bioassays, with mortality curves established using increasing PHEO concentrations ranging from 140.00 to 1000.00 μL kg-1. Behavior was evaluated based on walking distance, walking time, walking speed, walking time proportion, flight height, and flight takeoff success. Respiration was measured via the respiratory rate, while population growth (ri) was assessed through the instantaneous growth rate. All 11 populations of S. zeamais were susceptible to PHEO, showing no signs of resistance. The populations exhibited varying behavioral and physiological responses to sublethal exposure to PHEO, indicating different mitigation strategies. The results confirm that PHEO possesses insecticidal potential for controlling S. zeamais populations. However, the observed behavioral and physiological responses should be considered when establishing control measures in pest management programs for stored products.