BACKGROUND: The impact of age on the causes of death (CODs) in patients with early-stage intrahepatic cholangiocarcinoma (ICC) who had undergone surgery was analyzed in this study.
METHODS: A total of 1555 patients (885 in the older group and 670 in the younger group) were included in this study. Before and after applying inverse probability of treatment weighting (IPTW), the different CODs in the 2 groups were further investigated. Additionally, 7 different machine learning models were used as predictive tools to identify key variables, aiming to evaluate the therapeutic outcome in early ICC patients undergoing surgery.
RESULTS: Before (5.92 vs. 4.08 years, P < 0.001) and after (6.00 vs. 4.08 years, P < 0.001) IPTW, the younger group consistently showed longer overall survival (OS) compared with the older group. Before IPTW, there were no significant differences in cholangiocarcinoma-related deaths (CRDs, P = 0.7) and secondary malignant neoplasms (SMNs, P = 0.78) between the 2 groups. However, the younger group had a lower cumulative incidence of cardiovascular disease (CVD, P = 0.006) and other causes (P < 0.001) compared with the older group. After IPTW, there were no differences between the 2 groups in CRDs (P = 0.2), SMNs (P = 0.7), and CVD (P = 0.1). However, the younger group had a lower cumulative incidence of other CODs compared with the older group (P < 0.001). The random forest (RF) model showed the highest C-index of 0.703. Time-dependent variable importance bar plots showed that age was the most important factor affecting the 2-, 4-, and 6-year survival, followed by stage and size.
CONCLUSIONS: Our study confirmed that younger patients have longer OS compared with older patients. Further analysis of the CODs indicated that older patients are more likely to die from CVDs. The RF model demonstrated the best predictive performance and identified age as the most important factor affecting OS in early ICC patients undergoing surgery.

BACKGROUND: In the past, there has been a clear conclusion regarding the sole impact of serum neurofilament light chain (sNfL) levels or type 2 diabetes mellitus (DM) on the risk of death. However, the combined effect of sNfL levels and type 2 DM on all-cause and cardiovascular mortality is still uncertain.
METHODS: This study was a prospective cohort study based on data from the National Health and Nutrition Examination Survey (NHANES). The sNfL levels were measured through immunological methods using blood samples collected during the survey. The diagnosis of diabetes was based on rigorous criteria, and participants\' mortality data were followed up until December 31, 2019. Firstly, we separately examined the effects of sNfL and type 2 DM on all-cause and cardiovascular mortality, and finally studied the comprehensive impact of the combination of sNfL and type 2 DM on the risk of mortality. Cumulative Kaplan-Meier curves, multivariate logistic regression and sensitivity analysis were incorporated throughout the entire study.
RESULTS: Participants in the highest quartile of sNfL were observed. Multivariable COX regression model showed that increased sNfL levels and type 2 DM were respectively associated with an increased risk of all-cause and cardiovascular mortality. Furthermore, elevated sNfL levels were significantly associated with an increased risk of all-cause mortality and cardiovascular mortality after adjustment for confounding factors. When considering both elevated sNfL levels and type 2 DM, individuals had a significantly increased risk of mortality. Sensitivity analysis confirmed the robustness of the findings.
CONCLUSIONS: These results suggest that elevated levels of sNfL and type 2 DM are associated with an increased risk of all-cause and cardiovascular mortality, and that participants with increased sNfL levels associated with type 2 DM have higher all-cause mortality and cardiovascular mortality.

OBJECTIVE: To investigate relationships between prognostic nutritional index (PNI) during pregnancy and risk of all-cause mortality (ACM) and cardiovascular disease (CVD) mortality in persons with gestational diabetes mellitus (GDM).
METHODS: A cross-sectional study was conducted using NHANES data from 2007 to 2018, and weighted Cox regression models were established. Restricted cubic spline analysis was used to unveil associations of PNI with risk of ACM and CVD mortalities in individuals with GDM. Receiver operating characteristic curve was employed for determination of threshold value for association of PNI with mortality. Sensitivity analysis was performed to verify the stability of the results.
RESULTS: 734 GDM individuals and 7987 non-GDM individuals were included in this study. In GDM population, after adjusting for different categorical variables, PNI was significantly negatively correlated with ACM risk. Subgroup analysis showed that among GDM populations with no physical activity, moderate physical activity, parity of 1 or 2, negative correlation between PNI and risk of ACM was stronger than other subgroups. Sensitivity analysis results showed stable negative correlations between PNI and ACM and CVD mortality of total population, and between PNI and ACM of GDM.
CONCLUSIONS: In individuals with GDM, PNI was negatively correlated with ACM risk, especially in populations with no physical activity, moderate physical activity, and parity of 1 or 2. PNI = 50.75 may be an effective threshold affecting ACM risk in GDM, which may help in risk assessment and timely intervention for individuals with GDM.

BACKGROUND: The aim of this study was to investigate the association between systemic immune-inflammation index (SII) and all-cause mortality in individuals with chronic kidney disease (CKD).
METHODS: This prospective cohort study was carried out among 9303 participants with CKD from the National Health and Nutrition Examination Survey cycles spanning 1999 to 2018. The mortality data were ascertained by linking participant records to the National Death Index up to December 31, 2019. Complex sampling-weighted multivariate Cox proportional hazards models were employed to estimate the association between SII level and all-cause mortality, providing hazard ratios (HR) and 95% confidence intervals (CI). A restricted cubic spline analysis was conducted to explore potential nonlinear correlation. Subgroup analyses and sensitivity analyses were also conducted.
RESULTS: During a median follow-up period of 86 months, 3400 (36.54%) all-cause deaths were documented. A distinctive \"J\"-shaped relationship between SII level and all-cause mortality was discerned among individuals with CKD, with the nadir observed at an SII level of 478.93 within the second quartile. After adjusting for potential covariates, the risk of all-cause mortality escalated by 13% per increment of one standard deviation of SII, once SII exceeded 478.93 (HR = 1.13; 95% CI = 1.08-1.18). An elevated SII was associated with an increased risk of all-cause mortality among patients with CKD (Q4 vs. Q2: HR = 1.23; 95% CI = 1.01-1.48). Subgroup analyses indicated that the correlation between SII and CKD mortality was particularly pronounced among participants over 60 years old and individuals with diabetes. Sensitivity analyses revealed a linear positive association between SII and all-cause mortality after removing the extreme 5% outliers of SII.
CONCLUSIONS: A distinctive \"J\"-shaped relationship between SII level and all-cause mortality was identified among individuals with CKD. Further research is warranted to validate and expand upon these findings.

UNASSIGNED: To examine the associations of healthy lifestyles with risk of all-cause and cause-specific mortality among adults with metabolic dysfunction-associated steatotic liver disease (MASLD), and whether the association was mediated by systemic immune-inflammatory biomarkers (SIIBs).
UNASSIGNED: The study included 10,347 subjects with MASLD, who were enrolled in the Dongfeng-Tongji cohort study. The healthy lifestyles referred to non-smoking, being physically active (≥7.5 metabolic equivalents-hours/week), low-risk alcohol consumption (1-14 g/day for women and 1-28 g/day for men), and optimal sleep duration (≥6 to ≤8 h/day). Cox proportional hazard models were used to examine the relationship between each lifestyle and SIIBs with the risk of all-cause and cause-specific mortality. A mediation analysis was conducted to investigate the role of SIIBs on the association between healthy lifestyles and mortality.
UNASSIGNED: There were 418 MASLD subjects dead till the follow-up of 2018, including 259 deaths from cardiovascular disease (CVD). Compared to MASLD participants with 0-1 healthy lifestyle score (HLS), those with 3-4 HLS had the lowest risk of all-cause mortality [hazard ratio (HR), 0.46; 95% CI, (0.36-0.60)], and CVD mortality [HR (95%CI), 0.41 (0.29-0.58)]. Mediation analyses indicated that SIIBs mediated the association between healthy lifestyles and mortality, with proportions ranging from 2.5% to 6.1%.
UNASSIGNED: These findings suggest that adherence to healthy lifestyles can significantly reduce mortality for MASLD patients, and the decreased SIIBs may partially explain the protection mechanism of healthy lifestyles.

UNASSIGNED: No study has reported secular trends in dementia prevalence, all-cause mortality, and survival status in rural China.
UNASSIGNED: We established two cohorts (XRRCC1 and XRRCC2) in the same region of China, 17 years apart, to compare dementia prevalence, all-cause mortality, and survival status, and performed regression analysis to identify associated factors.
UNASSIGNED: Dementia prevalence was 3.49% in XRRCC1 and 4.25% in XRRCC2, with XRRCC2 showing a significantly higher prevalence (OR = 1.79, 95%CI: 1.2-2.65). All-cause mortality rates for dementia patients were 62.0% in XRRCC1 and 35.7% in XRRCC2. Mortality in the normal population of XRRCC2 decreased by 66% compared to XRRCC1, mainly due to improved survival rates in women with dementia. Dementia prevalence was positively associated with age >65, spouse-absent status, and stroke, and negatively associated with ≥6 years of education.
UNASSIGNED: Dementia prevalence in rural China increased over 17 years, while mortality decreased. Major risk factors include aging, no spouse, and stroke, with higher education offering some protection.

UNASSIGNED: To date, no studies have investigated the correlation between the neutrophil-to-lymphocyte ratio (NLR) and the long-term risk of mortality in individuals with both coronary heart disease (CHD) and hypertension. This study aims to evaluate the association between NLR and all-cause and cardiovascular mortality among this patient population.
UNASSIGNED: National Death Index (NDI) and National Health and Nutrition Examination Survey (NHANES 2001-2018) were the data sources. A nonlinear association between the NLR and mortality risk was shown by restricted cubic spline (RCS) analysis. Using a weighted Cox proportional hazards model, we quantitatively evaluated the effect of NLR on mortality risk.The capacity of NLR to forecast survival was assessed by evaluating time-dependent receiver operating characteristic (ROC) curves. A mediating influence analysis was conducted to assess the influence of NLR on mortality through eGFR as a mediator.
UNASSIGNED: The study involved a total of 2136 individuals. During the median follow-up interval of 76.0 months, 801 deaths were recorded. The RCS analysis showed NLR and mortality risk to have a nonlinear relationship. Two groups were established based on the participants\' NLR levels: a group with high NLR (NLR > 2.65) and a group with low NLR (NLR < 2.65). After adjusting for potential confounding factors, the Cox proportional hazards model revealed that participants with an increased NLR faced a significantly higher risk of cardiovascular mortality. (HR 1.58, 95% CI 1.33-1.82, p < 0.0001) and all-cause mortality (HR 1.46, 95% CI 1.30-1.62, p < 0.0001). An analysis of interactions and data stratification corroborated the validity of our findings. eGFR was identified as a partial mediator in the association between NLR and mortality rates, contributing 12.17% and 9.66% of the variance in all-cause and cardiovascular mortality, respectively. The predictive performance for cardiovascular mortality was quantified using ROC curves, with respective AUC values of 0.67, 0.65, and 0.64 for predictions over 3, 5, and 10 years. The AUC values for all-cause mortality were 0.66, 0.64, and 0.63 for the same time frames.
UNASSIGNED: For patients with CHD and hypertension, an elevated NLR serves as an independent prognostic indicator for both all-cause and cardiovascular mortality.

There is still a paucity of research on the relationship between triglyceride-glucose-body mass index (TyG-BMI) and long-term all-cause and cardiovascular disease (CVD) mortality in patients with chronic kidney disease (CKD). The objective of this study was to explore the relationship between the TyG-BMI index and mortality rate and to determine valuable predictive factors for the survival status of this population. Data were obtained from the National Health and Nutrition Examination Survey (NHANES 2001-2018) and the National Death Index (NDI). We used multivariate Cox regression and restricted cubic spline (RCS) to analyze the link between the TyG-BMI index and all-cause and CVD mortality. Subgroup analysis was conducted according to age, gender, race, education and poverty. In addition, receiver operating characteristic (ROC) curves were utilized to assess the differentiation of the TyG-BMI index in predicting mortality. A total of 3089 individuals were enrolled. Over a median follow-up period of 81 months, 1097 individuals passed away. The RCS analysis revealed a U-shaped link between the TyG-BMI index and all-cause and CVD mortality. The ROC curve indicated that the TyG-BMI index has a stronger diagnostic effect than the TyG index. Subgroup analysis results demonstrated that the TyG-BMI index was more significantly correlated with all-cause and CVD mortality rates in elderly patients. In the American population, a U-shaped association was discovered between the baseline TyG-BMI index and all-cause and cardiovascular mortality rates in CKD patients. The thresholds for all-cause and CVD mortality were found to be 299.31 and 294.85, respectively.

UNASSIGNED: Advanced chronic kidney disease (CKD) is common among patients with coronary artery disease (CAD), and angiotensin‑converting enzyme inhibitors (ACEI) or angiotensin‑receptor blockers (ARB) can improve cardiac and renal function, but whether ACEI/ARB therapy improves long-term prognosis remains unclear among these high-risk patients. Therefore, this research aimed to investigate the relationship between ACEI/ARB therapy and long-term prognosis among CAD patients with advanced CKD.
UNASSIGNED: CAD patients with advanced CKD were included in five hospitals. Advanced CKD was defined as estimated glomerular filtration rate (eGFR)<30 ml/min per 1.73 m2. Cox regression models and competing risk Fine and Gray models were used to examine the relationship between ACEI/ARB therapy and all-cause and cardiovascular death, respectively.
UNASSIGNED: Of 2527 patients, 47.6% population of our cohort was discharged on ACEI/ARB. The overall all-cause and cardiovascular mortality were 38.6% and 24.7%, respectively. Multivariate Cox regression analyses indicated that ACEI/ARB therapy was found to be associated with lower rates of both all-cause mortality (hazard ratio (HR)=0.836, 95% confidence interval (CI): 0.738-0.948, p = 0.005) and cardiovascular mortality (HR = 0.817, 95%CI: 0.699-0.956, p = 0.011). In the propensity-matched cohort, the survival benefit was consistent, and significantly better survival was observed for all-cause mortality (HR = 0.856, 95%CI: 0.752-0.974, p = 0.019) and cardiovascular mortality (HR = 0.830, 95%CI: 0.707-0.974, p = 0.023) among patients treated with ACEI/ARB.
UNASSIGNED: ACEI/ARB therapy showed a better survival benefit among high-risk CAD patients with advanced CKD at long-term follow-up, which manifested that strategies to maintain ACEI/ARB treatment may improve clinical outcomes among these high-risk populations.
What is the current knowledge on the topic? Advanced CKD is highly prevalent and strongly associated with higher mortality risk and worse outcomes among CAD patients, and patients with advanced CKD have often been excluded from randomized controlled trials, creating an evidence gap for these high-risk CAD patients. ACEI/ARB are beneficial for greater survival among CAD patients, but the effect of ACEI/ARB therapy on long-term prognosis is unclear among CAD patients with advanced CKD.What does this study add to our knowledge? ACEI/ARB treatment showed a better survival benefit among high-risk CAD patients with advanced CKD at long-term follow-up.How might this change clinical pharmacology or translational science? CAD patients with advanced CKD are not only have worse outcomes but also limited in their choice of therapy strategies. Our study may prompt an important reference for the subsequent improvement of long-term prognosis among these high-risk populations.

UNASSIGNED: The aim of this study was to investigate the relationship between triglyceride-glucose (TyG) index and cardiovascular disease (CVD) and all-cause mortality in adults with metabolic syndrome (MeS) and explore the mediating role of oxidative stress.
UNASSIGNED: This study included 6131 adults with MeS from the National Health and Nutrition Examination Survey (NHANES). The relationships between TyG index and mortality were elucidated using multivariate Cox proportional hazards models, restricted cubic splines (RCS) Fine-Gray competing risk model. In addition, mediation analysis was used to test the indirect effect of oxidative stress indicators.
UNASSIGNED: Over a median 106-month follow-up, a total of 357 CVD and 1292 all-cause deaths were recorded. After multivariate adjustment, there was a J-type relationship between TyG index and CVD and all-cause mortality, with optimal inflection point of 9.13 and 8.92. After the threshold point, TyG index was positively associated with CVD (HR: 4.21, 95%CI: 1.82, 9.78) and all-cause mortality(HR: 2.93, 95%CI: 2.05, 4.18). Even using non-cardiovascular mortality as a competitive risk, the Fine-Gray model also illustrated that the cumulative CVD mortality incidence was higher in MeS with TyG index >9.13 (Fine-Gray P< 0.01). Mediation analysis revealed that biomarkers of oxidative stress, including gamma-glutamyl transferase and uric acid, collectively mediated 10.53% of the association between the TyG index and CVD mortality, and 8.44% of the association with all-cause mortality (P < 0.05).
UNASSIGNED: In the cohort study, TyG index was found to have a J-shaped association with CVD mortality and all-cause mortality in MeS population and oxidative stress may play a key mediating role in this relationship.