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.

The aim of this study was to investigate all-cause mortality rates and related factors in patients with different levels of eosinophilia. This retrospective cohort study was conducted between January 2020 and December 2022 in the Internal Medicine Department of Dr Sadi Konuk Training and Research Hospital, Istanbul, Turkiye. A total of 161 patients with eosinophilia (at least 3 times) were included and divided into groups with absolute eosinophil counts of 500-999/µL (mild), 1000-1500/µL (moderate), and >1500/µL (severe). The mean age of patients was 65.67 ± 16.64 years at the time of admission, and 45 patients (57.8%) were male. The rates of mortality, oncological disease, and organ involvement were significantly higher in the severe group (P < .05). Increased serum total immunoglobulin E and vitamin B12, hematocrit value, eosinophil-to-lymphocyte ratio, and leukocyte were observed in eosinophilic patients. Decreased lymphocyte count, hemoglobin and hematocrit values were higher in deceased patients than in survivors (P < .05). Increased eosinophil-to-lymphocyte ratio, C-reactive protein, vitamin B12, and lactate dehydrogenase (LDH) activity were observed in participants who died compared to those who survived (P < .05). Multivariable logistic regression revealed that advanced age and higher LDH activity were independently associated with greater mortality risk while receiving non-steroid anti-inflammatory drugs or proton-pump inhibitors were associated with reduced mortality risk (P < .05). Advanced age and increased LDH activity were independently associated with greater risk for mortality, whereas absolute eosinophil counts was not. Considering the literature on this topic, our results show the need for further clinical and fundamental research to understand the role of eosinophils in human disease.

Sooty mangabeys (SMs) are natural hosts of simian immunodeficiency virus (SIV) and do not progress to AIDS despite high viral replication. The main factors involved in the benign nature of this infection are (i) low level of immune activation, (ii) relative preservation of specific CD4+ T-cell subsets from direct virus infection, and (iii) absence of microbial translocation from the gut to the systemic circulation. To determine the impact of SIV infection on underlying cause of death, we retrospectively analyzed data from 307 SMs (219 SIV infected and 88 uninfected) housed at the Emory Primate Center that have died between 1986 and 2022. Interestingly, we found that SIV-infected SMs live ~4 years longer than SIV-uninfected SMs, although this result is hard to interpret due to differences in how animals were housed and assigned to specific experimental studies. While the causes of death were not different between SIV-infected and uninfected SMs that died before age 15 (i.e., adult), we found significant differences in the relative frequency of specific causes of death in the elderly population (≥15 years old). Specifically, we observed that SIV-infected SMs were more likely to die from infections but less likely to die from cardiovascular disease (and diabetes in female animals) as compared to uninfected SMs. While confirming the non-pathogenic nature of SIV infection in SMs, these data reveal, for the first time, a qualitative impact of SIV infection on the host physiology that induces a significant change in the mortality pattern in these natural SIV hosts.
OBJECTIVE: In this study, we demonstrate, for the first time, that the natural, non-pathogenic SIV infection of the African monkey SM has a clinical impact which is revealed in terms of main causes of mortality, which are significantly different in the infected animals as compared to the uninfected ones. Indeed, SIV-infected SMs are at higher risk of dying of infectious diseases but appear to be somewhat protected from cardiovascular causes of death. The identification of a specific pattern of mortality associated with the infection suggests that the host-pathogen interaction between SIV and the SM immune system, while non-pathogenic in nature, has a detectable impact on the overall health status of the animals.

OBJECTIVE: To assess the trend in mortality rates and years of potential life lost (YPLL) due to suicide among adolescents in Northeast Brazil.
METHODS: This is an ecological time series study, with secondary data from 2011 to 2020 from the Mortality Information System for adolescents aged 10 to 19 years in the Northeast region of Brazil. Groups of causes from the 10th Revision of the International Classification of Diseases were included: X60-X84 (intentionally self-inflicted injuries), Y10-Y19 (poisoning of undetermined intent), and Y87 (sequelae of intentional self-harm). Mortality coefficients and frequency distribution by sociodemographic variables, place of occurrence, and method of suicide were estimates. YPLL were estimated by gender and age. Joinpoint regression analysis was used, and the annual percentage change (APC) was determined with 95% confidence intervals.
RESULTS: A total of 2,410 deaths were recorded, with a predominance of adolescents aged between 15 and 19, males, of mixed-race, low schooling, and home was the main place of occurrence. The trend in the death rate was increasing in the Northeast (APC: 3.6%; p = 0.001), in girls aged 10 to 14 (APC: 8.7%; p = 0.003), in boys aged 15 to 19 (APC: 4.6%; p = 0.002) and in Bahia (APC: 8.1%; p = 0.012). Hanging/strangulation was the main method adopted by both sexes. The YPLL due to suicide were 11,110 in 2011 and 14,960 in 2020.
CONCLUSIONS: The precociousness of suicide committed by girls and the increase in mortality among older adolescents are noteworthy, and specific preventive measures need to be adopted for these groups in order to reduce this preventable cause of death.

UNASSIGNED: Data on the increase in mortality during the COVID-19 pandemic based on individuals\' socioeconomic positions are limited. This study examines this increase in mortality in Spain during the epidemic waves of 2020 and 2021.
UNASSIGNED: We calculated the overall and cause-specific mortality rates during the 2017-2019 pre-pandemic period and four epidemic periods in 2020 and 2021 (first, second, third-fourth, and fifth-sixth waves). Mortality rates were analyzed based on educational levels (low, medium, and high) and across various age groups (25-64, 65-74, and 75+). The increase in mortality during each epidemic period compared to the pre-pandemic period was estimated using mortality rate ratios (MRR) derived from Poisson regression models.
UNASSIGNED: An inverse educational gradient in overall mortality was observed across all periods; however, this pattern was not consistent for COVID-19 mortality in some age groups. Among those aged 75 years and older, highly educated individuals showed higher COVID-19 mortality during the first wave. In the 25-64 age group, individuals with low education experienced the highest overall mortality increase, while those with high education had the lowest increase. The MRRs were 1.21 and 1.06 during the first wave and 1.12 and 0.97 during the last epidemic period. In the 65-74 age group, highly educated individuals showed the highest overall mortality increase during the first wave, whereas medium-educated individuals had the highest increase during the subsequent epidemic periods. Among those aged 75 and older, highly educated individuals exhibited the highest overall mortality increase while the individuals with low education showed the lowest overall mortality increment, except during the last epidemic period.
UNASSIGNED: The varying educational patterns of COVID-19 mortality across different age groups contributed to the disparities of findings in increased overall mortality by education levels during the COVID-19 pandemic.

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.

UNASSIGNED: Schizophrenia is associated with premature mortality from mostly natural causes. Decreased cognitive functioning has been identified as a determinant of mortality in the general population. However, there have been few prospective studies of this issue in persons with schizophrenia.
UNASSIGNED: To examine whether lower cognitive functioning is a risk factor for natural cause mortality in schizophrenia.
UNASSIGNED: This prospective cohort study included persons with schizophrenia or schizoaffective disorder enrolled between February 1, 1999, and December 31, 2022, at a nonprofit psychiatric system in Baltimore, Maryland. Participants were evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and other clinical measures.
UNASSIGNED: Natural cause mortality.
UNASSIGNED: Associations of cognitive function, obesity, tobacco smoking, and medical conditions with natural cause mortality were evaluated using Cox proportional hazards regression models.
UNASSIGNED: Of the 844 participants enrolled (mean [SD] age, 39.6 [12.1] years; 533 male [63.2%]), 158 (18.7%) died of natural causes during a median follow-up of 14.4 years (range, 7.0 days to 23.9 years). The most significant factor associated with mortality was lower cognitive functioning as measured by the RBANS (Cox coefficient, -0.04; 95% CI, -0.05 to -0.03; z = -5.72; adjusted P < .001). Additional factors independently associated with mortality included the diagnosis of an autoimmune disorder (hazard ratio [HR], 2.86; 95% CI, 1.83-4.47; z = 4.62; adjusted P < .001), tobacco smoking (HR, 2.26; 95% CI, 1.55-3.30; z = 4.23; adjusted P < .001), diagnosis of chronic obstructive pulmonary disease (HR, 3.31; 95% CI, 1.69-6.49; z = 3.48; adjusted P = .006), body mass index as a continuous variable (HR, 1.06; 95% CI, 1.02-1.09; z = 3.30; adjusted P = .01), diagnosis of a cardiac rhythm disorder (HR, 2.56; 95% CI, 1.40-4.69; z = 3.06; adjusted P = .02), and being divorced or separated (HR, 1.80; 95% CI, 1.22-2.65; z = 2.97; adjusted P = .02). An RBANS score below the 50th percentile displayed a joint association with being a smoker, having an elevated body mass index, and having a diagnosis of an autoimmune or a cardiac rhythm disorder.
UNASSIGNED: In this prospective cohort study, lower cognitive functioning was a risk factor for natural cause mortality in schizophrenia. Efforts should be directed at methods to improve cognitive functioning, particularly among individuals with additional risk factors.

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.

BACKGROUND: As the Sustainable Development Goal 3.2.1 deadline (2030) approaches, rapidly reducing under-5 mortality (U5M) gains more prominence. However, initiatives or interventions that aided Bangladesh in achieving Millennium Development Goal 4 showed varied effectiveness in reducing certain cause-specific U5M. Therefore, this study aimed to examine the predictors of the key cause-specific mortalities.
METHODS: This cross-sectional study was conducted using the Bangladesh Demographic and Health Survey 2011 and 2017-18 data. Cause-specific U5M was examined using multilevel multinomial mixed-effects analyses, and overall/all-cause U5M was examined using multilevel mixed-effects analyses. The respective estimates were compared.
RESULTS: The cause-specific analysis revealed that pneumonia and prematurity-related U5M were significantly associated with antenatal care and postnatal care, respectively. However, analysis of overall/all-cause U5M did not reveal any significant association with health services. Twins or multiples had a greater risk of mortality from preterm-related conditions (adjusted Relative Risk Ratio (aRRR): 38.01, 95% CI: 19.08-75.7, p < .001), birth asphyxia (aRRR: 6.52, 95% CI: 2.51-16.91, p < .001), and possible serious infections (aRRR: 11.12, 95% CI: 4.52-27.36, p < .001) than singletons. Children born to mothers 18 years or younger also exhibited a greater risk of mortality from these three causes than children born to older mothers. This study also revealed an increase in the predicted risk of prematurity-related mortality in the 2017-18 survey among children born to mothers 18 years or younger, children born to mothers without any formal education, twins or multiples and children who did not receive postnatal care.
CONCLUSIONS: This research provides valuable insights into accelerating U5M reduction; a higher risk of preterm-related death among twins underscores the importance of careful monitoring of mothers pregnant with twins or multiples through the continuum of care; elevated risk of death among children who did not receive postnatal care, or whose mothers did not receive antenatal care stresses the need to strengthen the coverage and quality of maternal and neonatal health care; furthermore, higher risks of preterm-related deaths among the children of mothers with low formal education or children born to mothers 18 years or younger highlight the importance of more comprehensive initiatives to promote maternal education and prevent adolescent pregnancy.