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Background: Breast cancer remains the most prevalent malignancy and the leading cause of cancer-related mortality among women worldwide. The primary factors contributing to the deterioration and death of patients with breast cancer are metastasis, recurrence, and drug resistance. These phenomena are closely related to the presence of breast cancer stem cells; however, the exact mechanisms regulating stemness remain to be elucidated. Rack1 (Receptor for Activated C Kinase 1), a well-known versatile scaffold protein, has been implicated in tumorigenesis and progression in numerous cancer types; however, its specific role in breast cancer stemness remains to be elucidated. Methods: Using bioinformatic and immunohistochemical approaches, we validated that the expression level of Rack1 is associated with cancer stemness and affects the prognosis of patients. Through a series of experimental methods including mammosphere formation assay, flow cytometry, qPCR, Western blotting, and CHX assays, we validated at the molecular and cellular levels the mechanism by which Rack1 influences cancer stemness via the E2F1/SOX2 axis. Furthermore, by designing and utilizing lentiviral constructs to establish xenograft tumor models in mice, we further confirmed in vivo the impact of the Rack1/E2F1/SOX2 axis on the tumorigenic capacity of breast cancer cells. Results: Our findings indicate that Rack1 plays a critical role in preserving the stemness characteristics of breast cancer cells. Mechanistically, the observed effects of Rack1 are achieved through the modulation of SOX2 expression, a master transcription factor that regulates cancer cell stemness and maintenance. We further demonstrate that Rack1 increases the stability of the E2F1 protein by inhibiting its ubiquitination and subsequent proteasome-mediated degradation, which in turn transcriptionally upregulates SOX2, thereby maintaining breast cancer cell stemness and tumorigenesis. Conclusion: This study thus unveils a novel mechanism through which Rack1 executes its oncogenic function. This study also demonstrates that targeting the Rack1-E2F-SOX2 axis may be a potential strategy to inhibit breast cancer development and progression. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption has been associated with an increased risk of cancer-related mortality. It may also negatively impact oncological therapies, potentially leading to impaired effectiveness or an increased risk of treatment-related toxicities. The aim of this systematic review and meta-analysis was to examine the current evidence regarding the potential effects of alcohol consumption during cancer treatments on both treatment effectiveness and toxicity, irrespective of cancer type. Methods: A comprehensive literature search was performed across three electronic databases (Medline, Web of Science, Cochrane) covering studies from January 1990 to December 2023. Furthermore, a manual search based on the reference lists of the eligible studies was performed to identify additional potentially eligible studies. Studies were eligible if they involved cancer patients and provided data on alcohol consumption during specific oncological treatments, including its effect on treatment outcomes, or compared treatment effectiveness or toxicity between drinkers and non-drinkers. Studies were excluded if they did not meet these criteria, were duplicates, case reports, conference abstracts, or focused only on cancer-specific or overall survival. Only studies using multivariable analyses to examine the association between alcohol consumption and treatment effectiveness or toxicity were included in the pooled analyses. Pooled Hazard Ratios (HRs) or Odds Ratios (ORs) and their corresponding 95% Confidence Intervals (CIs) were calculated using random-effects models. Study quality was assessed by using the Newcastle–Ottawa scale whereas the GRADE approach was applied to rate the certainty of evidence for pooled analyses. Results: Out of 6734 studies identified through searching, 38 met the inclusion criteria for pooled analyses. Alcohol consumption during radiotherapy, with or without concomitant chemotherapy, was associated with worse disease-free survival (pooled HR: 2.05; 95% CI: 1.09 – 3.89), although the numerically increased risk for locoregional recurrence did not reach statistically significance (pooled HR: 2.01; 95% CI: 0.76 – 5.36). The potential impact of alcohol consumption on chemotherapy-induced neurotoxicity and acute / delayed nausea was not statistically significant. However, alcohol consumption was associated with a lower risk of overall chemotherapy-induced nausea (OR: 0.69; 95% CI: 0.57, 0.84). Conclusion: Our findings suggest that alcohol consumption may have a negative impact on radiotherapy, whereas its potential impact on the effectiveness of systemic oncological therapies (chemotherapy, molecular targeted therapy, immunotherapy, endocrine therapy) has not been adequately studied. Similarly, the current evidence on the potential association between alcohol consumption and treatment-related toxicities is weak, highlighting the need for well-designed prospective studies on this topic. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) poses significant challenges globally, ranking fifth in incidence and fourth in cancer-related mortality. SALL4, a stem cell transcription factor with multiple isoforms, includes SALL4-A as its full-length form. This study aims to evaluate the diagnostic potential of SALL4-A isoform expression in GC and its clinical significance. Method: Immunohistochemical (IHC) analysis was conducted on Tissue Micro Array (TMA) slides from 167 GC patients. Clinicopathological parameters were correlated with SALL4-A expression, and survival analysis was performed. Diagnostic performance was assessed using metrics such as sensitivity, specificity, and area under the curve (AUC). Results: SALL4-A exhibited distinct cytoplasmic expression in GC, correlating with lower histological grade (p = 0.003) and TNM stage (p = 0.003), particularly in the intestinal subtype. Diagnostic evaluation showed an AUC of 0.803 for cytoplasmic expression, demonstrating high diagnostic potential. However, SALL4-A expression did not show significant prognostic value. Conclusion: Cytoplasmic SALL4-A expression in GC is associated with less aggressive tumor phenotypes and shows promise as a diagnostic marker. Further research is warranted to elucidate its mechanistic role and potential integration into clinical practice. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is the 12th most common type of cancer, and the sixth leading cause of cancer-related mortality, worldwide. Up-to-date statistics on pancreatic cancer would provide us with a better understanding of epidemiology and identify the causative risk factors for the prevention of this disease. Methods: The degree and change patterns of exposure as well as the attributable cancer burden, including incidence, mortality, disability-adjusted life years (DALYs), and prevalence in global and regional, by sex, age, year, for pancreatic cancer, with the data extracted from the Global Burden of Diseases Study (GBD) 2021. All data analyses were conducted using linear regression analysis and the Joinpoint software (version 5.0.1). Results: In 2021, 508,533 new cases of pancreatic cancer have been reported; the mortality and prevalence rate increased to 5.95, and 5.12 respectively; and the global DALYs rate increased to 130.33 this year. Besides, the pancreatic cancer-associated rates of incidence, mortality, DALYs, and prevalence were higher in males than in females. In addition, these indicators in the high SDI (Sociodemographic index) region were higher than the global mean. To date, the high fasting plasma glucose remained the major risk factor that influenced the incidence, mortality, DALYs, and prevalence of pancreatic cancer, followed by tobacco and high body mass index (BMI). Conclusions: Results of this study suggest that the burden of pancreatic cancer is increasing generally, therefore, more attention and measures should be taken to cope with this situation. [ABSTRACT FROM AUTHOR]

Background: To effectively monitor long-term outcomes among cancer patients, it is critical to accurately assess patients' dynamic prognosis, which often involves utilizing multiple data sources (e.g., tumor registries, treatment histories, and patient-reported outcomes). However, challenges arise in selecting features to predict patient outcomes from high-dimensional data, aligning longitudinal measurements from multiple sources, and evaluating dynamic model performance. Methods: We provide a framework for dynamic risk prediction using the penalized landmark supermodel (penLM) and develop novel metrics ( and ) to evaluate and summarize model performance across different timepoints. Through simulations, we assess the coverage of the proposed metrics' confidence intervals under various scenarios. We applied penLM to predict the updated 5-year risk of lung cancer mortality at diagnosis and for subsequent years by combining data from SEER registries (2007–2018), Medicare claims (2007–2018), Medicare Health Outcome Survey (2006–2018), and U.S. Census (1990–2010). Results: The simulations confirmed valid coverage (~ 95%) of the confidence intervals of the proposed summary metrics. Of 4,670 lung cancer patients, 41.5% died from lung cancer. Using penLM, the key features to predict lung cancer mortality included long-term lung cancer treatments, minority races, regions with low education attainment or racial segregation, and various patient-reported outcomes beyond cancer staging and tumor characteristics. When evaluated using the proposed metrics, the penLM model developed using multi-source data ( of 0.77 [95% confidence interval: 0.74–0.79]) outperformed those developed using single-source data ( range: 0.50–0.74). Conclusions: The proposed penLM framework with novel evaluation metrics offers effective dynamic risk prediction when leveraging high-dimensional multi-source longitudinal data. [ABSTRACT FROM AUTHOR]

Background: Evidence is lacking on whether chronic pain is related to the risk of cancer mortality. This study seeks to unveil the association between chronic pain and all-cause, cancer, as well as non-cancer death in cancer patients based on the National Health and Nutrition Examination Survey (NHANES) database. Methods: Cancer survivors aged at least 20 (n = 1369) from 3 NHANES (1999–2004) cycles were encompassed. Chronic pain and cancer were determined through self-report. We employed records from the National Death Index for the determination of death status and reason. All-cause, cancer, and non-cancer deaths were primary outcomes. We used time-dependent ROC curve assessment to evaluate the predictive value of chronic pain for death in cancer patients. Results: Over a median 141-month follow-up (interquartile range: 61–201 months), 884 (64.57%) of 1,369 cancer sufferers died, of which 259 (18.91%) died from cancer, and 625 (45.65%) from other causes. Compared with non-chronic pain survivors, chronic pain correlated with elevated all-cause mortality (Hazard Ratio (HR), 1.40; 95% CI, 1.14–1.72, p = 0.001) and cancer death (HR, 1.75; 95% CI, 1.16–2.64, p = 0.008), primarily in patients with pain lasting 3 months or more. Chronic pain was related to higher non-cancer mortality (HR, 1.38; 95% CI, 1.04–1.82, p = 0.025), and no significant results were found in pain duration. Time-dependent ROC curves showed the area under the curve (AUC) for all-cause mortality at 1, 3, 5, 10, and 20-year survival for chronic pain of 0.71, 0.78, 0.84, 0.89, and 0.96, respectively. The AUCs for cancer mortality at 1, 3, 5, 10, and 20-year for chronic pain were 0.83, 0.87, 0.91, 0.94, and 0.95, respectively, and those for non-cancer mortality at 1, 3, 5, 10, and 20-year for chronic pain were 0.82, 0.86, 0.90, 0.91, and 0.97, respectively. Conclusion: Chronic pain is associated with heightened all-cause and cancer mortality in the cancer population. Clinical staff should focus on chronic pain in this patient population. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is a leading cause of mortality worldwide. The third most prevalent gynecological cancer globally, following cervical and uterine cancer, and the third leading cause of cancer-related mortality among women in Sub-Saharan Africa, including Ethiopia. The time ovarian cancer patients have to wait between diagnosis and initiation of treatment are the indicators of quality in cancer care and influence patient outcomes. Despite extensive studies in the field, little is known about the strength of the association between ovarian cancer survival and waiting time. So, the main purpose of this study is to assess the effect of waiting time on ovarian cancer survival in oncology centers in Addis Ababa, Ethiopia. Methods: A facility-based retrospective cohort study was conducted with a total of 561 study participants included. The main outcome of interest for this study was death due to ovarian cancer. The authors compared the ovarian cancer patients with waiting times ≤ 10 weeks and waiting times > 10 weeks for overall survival rate using the log rank test. The incidence density rate of mortality was calculated for each group variable. The effect of waiting time on ovarian cancer mortality was estimated using the Cox proportional hazards model at the 5% level of significance. Results: The incidence density rate of mortality among ovarian cancer patients for waiting time ≤ 10 weeks was found to be 10.85 (95%CI, 9.10-12.98) per 1,000 person years observation, while for waiting time > 10 weeks the mortality rate was found to be 18.05 (95%CI, 15.33–21.23) per 1,000 person years observation. In the Cox regression analysis after full adjustments for confounder variables, the mortality event risk was 36% higher among waiting time > 10 weeks women (AHR = 1.36; 95%CI = 1.05–1.75) as compared to waiting time ≤ 10 weeks. Conclusions: We have found that the incidence density rate of mortality among ovarian cancer patients was significantly higher in waiting time > 10 weeks groups. Therefore, future policy and clinician programmers should consider the impact of waiting time from diagnosis until to get the first treatment more carefully. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the leading cause of cancer-related mortality in women. Deregulation of miRNAs is frequently observed in breast cancer and affects tumor biology. A pre-miRNA, such as pre-miR-1307, gives rise to several mature miRNA molecules with distinct functions. However, the impact of global deregulation of pre-miR-1307 and its individual mature miRNAs in breast cancer has not been investigated in breast cancer, yet. Results: Here, we found significant upregulation of three mature miRNA species derived from pre-miR-1307 in human breast cancer tissue. Surprisingly, the overexpression of pre-miR-1307 in breast cancer cell lines resulted in reduced xenograft growth and impaired angiogenesis. Mechanistically, overexpression of miR-1307-5p altered the secretome of breast cancer cells and reduced endothelial cell sprouting. Consistently, expression of miR-1307-5p was inversely correlated with endothelial cell fractions in human breast tumors pointing at an anti-angiogenic role of miR-1307-5p. Importantly, the arm usage of miR-1307 and other miRNAs was highly correlated, which suggests an undefined common regulatory mechanism. Conclusions: In summary, miR-1307-5p reduces angiogenesis in breast cancer, thereby antagonizing the oncogenic effects of miR-1307-3p. Our results emphasize the importance of future research on the regulation of miRNA arm selection in cancer. The underlying mechanisms might inspire new therapeutic strategies aimed at shifting the balance towards tumor-suppressive miRNA species. [ABSTRACT FROM AUTHOR]

Background: Platelet count and function may be closely related to survival and prognosis of stroke and cancer. However, little is known on the impact of platelet count on the patients with a history of stroke and cancer. This study aimed to examine the association between baseline platelet level and all-cause mortality in this population using a cross-sectional analysis. Methods: Participants with a history of stroke and cancer were selected from the database of the National Health and Nutrition Examination Survey from 2007 to 2018. A maximum selected rank statistic was conducted to determine platelet cutoff with the most significant association with mortality. The association between platelet and mortality was characterized visually using restricted cubic spline (RCS). Weighted multivariable Cox regression models were performed to evaluate the association between platelet count and mortality. Time-dependent receiver operating characteristic (ROC) analysis was conducted to assess the accuracy of platelet count in predicting mortality. Results: Forty-three (43/113, 38.05%) stroke patients with cancer were alive at a median follow-up of 42 months (interquartile range, 23–74 months). The RCS analysis demonstrated a linear relationship between platelet and mortality (nonlinear, p = 0.352). Mortality in higher-platelet group (> 209 × 109/L, n = 57) was decreased than lower-platelet group (≤ 209 × 109/L, n = 56) (Model 1 HR 0.43, 95% CI 0.24—0.77, p = 0.005) (Model 2 HR 0.58, 95% CI 0.35—0.96, p = 0.03). Subgroup analyses showed no significant interaction between platelet and age, sex, BMI, WBC and neutrophil. The areas under time-dependent ROC curve of the 1-, 2-, 3-, 4- and 5-year survival rates were 0.54, 0.55, 0.57, 0.53, 0.59 for mortality of stroke patients with cancer. Conclusions: Lower platelet count may be an independent predictor of all-cause mortality in population with a history of stroke and cancer. This result may provide valuable insights for the long-term management in stroke patients with cancer. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer is a significant cause of mortality globally, with several factors impacting patient outcomes, including access to healthcare, early detection, and treatment. Despite this, the specific factors affecting incidence of death among colorectal cancer patients in the Amhara region have not been thoroughly investigated. Thus, this study seeks to assess incidence and determinants of mortality among colorectal cancer patients in Amhara Region oncology centers. Results: The mean age of the participants was 48.6 years (SD ± 15). Median survival time was 23.8 months. The overall incidence rate or incidence density of a colorectal cancer mortality rate was 2.9 per 100 person-months (95% CI: 2.5–3.4). Survival rates of colorectal cancer patients 1and 5 year was 69.78% and 16.1%, respectively. The result of the multivariable analysis showed that colorectal cancer patients who had presenting symptoms [AHR = 2.67 (95% CI: 1.95, 3.67)], Base line HGB level < 12.5 mg/dl [AHR = 1.63 (95% CI: 1.12, 2.37)], WHO or ECOG poor performance status [AHR = 2.99 (95% CI: 2.17, 4.12), late stage of cancer [AHR = 2.32 (95% CI: 1.42, 3.79)] and location of tumor on colorectal [AHR = 1.76 (95% CI: 1.20, 2.55)] were significantly associated with mortality of colorectal cancer. Conclusion and recommendation: The study highlights significant findings on the survival and mortality of colorectal cancer patients. The overall mortality rate was 2.9 per 100 person-months. Multivariable analysis identified presenting symptoms, low baseline hemoglobin levels, poor performance status, late-stage cancer, and tumor location as significant predictors of mortality. Highlighting the need for early detection and targeted care strategies. [ABSTRACT FROM AUTHOR]

Background: Smoking is a pivotal modifiable risk factor for lung cancer (LC). Previous studies have indicated that a smoking cessation program might be incorporated into the LC screening program. However, the effects of smoking cessation and its duration with the age at onset (AAO) of LC, all-cause mortality, and LC-specific mortality remain unclear. We aimed to comprehensively investigate the association of smoking cessation-related behaviors on the AAO of LC, LC-specific and all-cause mortality. Methods: A total of 2671 smokers with LC as the primary site from the UK Biobank were included in this study, with a 7:3 ratio assigned randomly to a discovery set (n = 1872) and a validation set (n = 799). Generalized linear regression models were used for AAO of LC outcomes and Cox models for mortality outcomes. Results: Participants over 60 years old could still benefit from smoking cessation to prolong AAOs (β = 1.613 for men, P = 0.003; β = 1.533 for women, P = 0.018). A cessation duration of > 15 years was associated with a later AAO in men (P < 0.001). Moreover, smoking cessation before 60 years old, especially among those under 40 years, was significantly associated with a lower risk of all-cause mortality (men: hazard ratio (HR): 0.65 [95% confidence interval 0.51–0.83]; women: 0.62 [0.47–0.83]) and LC-specific mortality (men: 0.67 [0.51–0.87]; women: 0.68 [0.50–0.92]). Compared with continuous smokers, former smokers who quit smoking for more than 15 years had a lower risk of all-cause mortality (men: 0.70 [0.59–0.84]; women: 0.68 [0.56–0.84]) and LC-specific mortality (men: 0.71 [0.59–0.87]; women: 0.69 [0.56–0.86]). Conclusions: Smoking cessation after 60 years old may still be helpful for a later AAO of LC. Former smokers who quit smoking for more than 15 years have a reduced risk of developing LC and mortality. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a major global public health concern and a major cause of cancer-related mortality. In 2020, 8.3% of the total breast cancer deaths worldwide were reported from China, which highlighted the need to understand the epidemiological trends of breast cancer within the country. Therefore, this study aimed to analyse the trends in the breast cancer burden in China from 1990 to 2021 and compare them with global trends to provide insights for future prevention and control strategies. Methods: Data were sourced from the Global Burden of Disease database 2021, which includes comprehensive information on the disease burden across 204 countries from 1990 to 2021. We analysed six key indicators: the mortality, prevalence, incidence, disability-adjusted life years, years lived with disability, and years of life lost. Age-standardized rates were analysed using the global age structure as a reference. Joinpoint regression was employed to assess the annual percentage change and average annual percentage change. Results: In 2021, 3.75 million prevalent breast cancer cases, with 385,837 new breast cancer cases and 88,106 deaths due to breast cancer, were reported from China. The crude rates of the prevalence, incidence, mortality, disability-adjusted life years, years lived with disability, and years of life lost significantly increased in 2021 compared with 1990. The age-standardized rates per 100,000 women were 355.72 for prevalence (+ 103.22% from 1990), 37.00 for incidence (107.40%), 8.24 for mortality (-8.24%), 281.54 for disability-adjusted life years (-6.68%), 25.86 for years lived with disability (110.24%), and 255.69 for years of life lost (-11.62%). The burden of breast cancer has notably increased among the women above 40 years of age, peaking between the ages of 50 and 59 years, and the proportion of cases in women under 40 years has decreased. Conclusions: The age-standardized rate of the mortality, disability-adjusted life years, and years of life lost of breast cancer decreased slightly in China; however, the age-standardized rate of the incidence, prevalence, and years lived with disability exhibited an upward trend between 1990 and 2021, thereby highlighting the need to improve treatment outcomes and formulate better policies for the prevention and control of breast cancer in China. [ABSTRACT FROM AUTHOR]

Background and objective: Esophageal cancer (EC) is the seventh most prevalent cancer globally and the sixth leading cause of cancer-related mortality. This study aimed to provide an updated stratified assessment of rates in EC incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 by sex, age, and Socio-demographic Index (SDI) at global, regional, and national levels, as well as to project the future trends of EC both globally and regionally. Methods: Data about age-standardized rates (ASRs) of incidence (ASIR), mortality (ASDR), probability of death (ASPoD) and DALYs (ASDALYRs) of EC were obtained from the 2021 Global Burden of Disease (GBD) study. Estimated annual percentage changes (EAPCs) and average annual percentage changes (AAPC) were calculated over certain periods to describe the temporal trends of EC burdens. The analyses were disaggregated by sexes, GBD super-regions and regions, nations/territories, age-groups, and SDI quintiles. A Bayesian age-period-cohort (BAPC) model was constructed to project the global and regional EC ASRs in 2022–2035. Results: Despite global reductions in EC ASRs, with ASIR, ASDR, and ASDALYR in 2021 of 6.65 [5.88, 7.45] (95% uncertainty interval), 6.25 [5.53, 7.00], and 148.56 [131.71, 166.82], decreasing by 24.9%, 30.7%, and 36.9% in 1990–2021, respectively, the absolute burden numbers were increased from 1990 to 2021, probably because of population growth and aging. Global newly diagnosed cases, deaths, and DALYs of EC increased to 576,529 [509,492, 645,648], 356,263 [319,363, 390,154], and 12,999,265 [11,522,861, 14,605,268] in 2021, by 62.53%, 51.18%, and 33.28% compared to records in 1990. The geographical pattern of EC was consistent: locations with the highest EC incidence and mortality rates were predominantly located in the Asian Esophageal Cancer Belt and African Esophageal Cancer Corridor, with East Asia, Southern Sub-Saharan Africa, and Eastern Sub-Saharan Africa as the GBD regions with the heaviest EC burdens, and Malawi, Eswatini, Mongolia, Zambia, and Zimbabwe with the most EC ASRs in 2021. However, owing to the population size, China, India, the United States, Japan, and Brazil had the heaviest absolute EC burdens. More pronounced alleviations of ASRs were observed in locations with high SDI levels, indicated by their lower AAPC values compared to those of low-SDI locations, while Sub-Saharan Africa regions had increasing EC ASRs, especially in Chad (114.76% in ASDR, for example), Sao Tome and Principe (97.93%), Togo (92.53%), Northern Mariana Islands (84.32%), Liberia (82.33%), etc. Smoking remained the leading contributor to EC ASDALYR globally and across most GBD super-regions in 2021. The EC burden is significantly heavier for males, with incidence and mortality in males in 2021 being 2.89 and 2.88 times higher, respectively, than in females. Across all age groups, EC posed an increasingly significant threat to men aged > 75 years. From 2022 to 2035, the ASR projections show only modest decrease in both global and regional EC burdens, and the absolute burden numbers are expected to increase globally and in nearly all GBD super-regions. Conclusion: EC burden remains significant, with disparities across sexes, age groups, and regions. Region-specific and age-targeted measures are crucial to addressing these inequalities, especially in light of increasing EC burdens in older men and in African regions. Efforts should be taken in finding more solid attributions to risk factors for EC burdens and to better identify high-risk populations to inform targeted prevention and screening, and ultimately reduce the EC burden in an efficient and cost-effective way. [ABSTRACT FROM AUTHOR]

Background: With metabolic disorders on the rise globally, the cardiometabolic index (CMI) has emerged as a crucial predictor of mortality risks linked to cancer, cardiovascular disease, and diabetes. This novel index, which combines lipid metabolism and body composition, is the focus of this study, aimed at exploring its association with all-cause and specific mortality in an all-age adult population. Methods: A longitudinal cohort study including 5,728 participants aged over 18 from nine cycles between 2001 and 2018 was enrolled and assessed. CMI served as the exposure variable, while outcomes included all-cause mortality and mortality due to cardiovascular disease, cancer, and diabetes. The Cox frailty model and average marginal effects were employed to evaluate the contribution of CMI to all-cause and specific mortality collectively. Restricted cubic spline analyses and stratified analyses were conducted to investigate potential nonlinear effects and interactions. Results: The decreased participants exhibited considerably higher CMI than the alive's. A positive association was found between CMI and all-cause mortality (HR=1.05, 95% CI=1.01-1.10). Notably, CMI was linked to an increased risk of cancer mortality (HR=1.02) and a reduced risk of cardiovascular disease mortality (HR=0.85). Furthermore, the average marginal effect of CMI on diabetes mortality was the largest (AME=0.499). The RCS curves revealed that participants had the lowest risk of all-cause mortality at a CMI of 0.618. Sensitivity analyses further supported these findings. Conclusion: This study represents the first comprehensive assessment on the contribution of CMI to mortality across an all-age adult population, providing some insights for the comprehensive assessment of health and disease states. [ABSTRACT FROM AUTHOR]

Background: Cancer is one of the leading causes of death in children and adolescents, with a significant concentration in low and middle-income countries. Previous research has identified disparities in cancer incidence and mortality based on a country's level of development. The Middle East and North Africa (MENA) region comprises of countries with heterogeneous income and development levels. This study aims to investigate whether discrepancies in cancer incidence and mortality among children and adolescents exist in countries within the MENA region. Materials and methods: Data on cancer incidence and mortality were drawn from the Global Burden of Disease Study (GBD) 2019 for all malignant neoplasms (including non-melanoma skin cancers). The analysis was restricted to children and adolescents aged less than 20 years. Mortality- to-Incidence ratios (MIR) were calculated as a proxy measure of survival for each cancer type and country and Spearman's correlation coefficient measured the association between socio-demographic index (SDI), incidence rates, mortality rates, and MIR. Results: In 2019, cancer incidence in the MENA region was 4.82/100,000 population, while mortality rate was 11.65/100,000 population. Cancer incidence and mortality was higher among males compared to females. A marked difference was observed in cancer-related mortality rates between low-income and high-income countries. MIR was higher in low-income countries, particularly for males and specific cancer types such as liver, colon and rectum, brain and central nervous system (CNS) cancers, and non-Hodgkin lymphoma among others. A negative correlation was observed between a country's SDI and MIR (-0.797) and SDI and mortality rates (-0.547) indicating that higher SDI corresponds to lower MIR and lower mortality rates. Conclusion: These findings highlight the need for evidence-based interventions to reduce cancer-related mortality and disease burden among children and adolescents, particularly in low-income countries within the region and for cancer types with the highest mortality rates. Additionally, efforts should focus on establishing registries to provide up-to-date national data on cancer incidence and mortality in countries within the region. [ABSTRACT FROM AUTHOR]

Background: Cardiometabolic index (CMI) is a comprehensive clinical parameter which integrates overweight and abnormal lipid metabolism. However, its relationship with all-cause, cardiovascular disease (CVD), and cancer mortality is still obscure. Thus, a large-scale cohort study was conducted to illustrate the causal relation between CMI and CVD, cancer, and all-cause mortality among the common American population. Methods: Our research was performed on the basis of National Health and Nutrition Examination Survey (NHANES) database, involving 40,275 participants ranging from 1999 to 2018. The formula of CMI is [waist circumference (cm) / height (cm)] × [triglyceride (mg/dL) / high-density lipoprotein cholesterol (mg/dL)]. Outcome variables consisted of CVD, cancer, and all-cause mortality, which were identified by the International Classification of Diseases (ICD)-10. The correlation between CMI and mortality outcomes was analyzed utilizing the Kaplan–Meier survival modeling, univariate/multivariate Cox regression analysis, smooth curve fitting analysis, threshold effect analysis, and subgroup analysis. Stratification factors for subgroups included age, race/ethnicity, sex, smoking behavior, drinking behavior, BMI, hypertension, and diabetes. Results: The baseline characteristics table includes 4,569 all-cause-induced death cases, 1,113 CVD-induced death cases, and 1,066 cancer-induced death cases. Without adjustment for potential covariates, significantly positive causal correlation existed between CMI and all-cause mortality (HR = 1.03, 95% CI 1.02,1.04, P-value<0.05), CVD mortality (HR = 1.04, 95% CI 1.03, 1.05, P-value<0.05) and cancer mortality(HR = 1.03, 95% CI 1.02, 1.05, P-value<0.05); whereas, after confounding factors were completely adjusted, the relationship lost statistical significance in CMI subgroups (P for trend>0.05). Subgroup analysis found no specific subgroups. Under a fully adjusted model, a threshold effect analysis was performed combined with smooth curve fitting, and the findings suggested an L-shaped nonlinear association within CMI and all-cause mortality (the Inflection point was 0.98); in particular, when the baseline CMI was below 0.98, there existed a negative correlation with all-cause mortality with significance (HR 0.59, 95% CI 0.43, 0.82, P-value<0.05). A nonlinear relation was observed between CMI and CVD mortality. Whereas, the correlation between CMI and cancer mortality was linear. Conclusions: Among the general American population, baseline CMI levels exhibited an L-shaped nonlinear relationship with all-cause mortality, and the threshold value was 0.98. What's more, CMI may become an effective indicator for CVD, cancer, and all-cause mortality prediction. Further investigation is essential to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: High red meat consumption is a main modifiable risk factor for colorectal cancer mortality (CRC), but its attributable disease burden remains unclear in China. We aimed to analyze the temporal trends in CRC deaths and disability-adjusted life years (DALYs) attributable to high red meat consumption in China from 1990 to 2021 and to predict the disease burden in the next 15 years. Methods: Data was obtained from the Global Burden of Disease (GBD) 2021 study. The Joinpoint regression model was used to calculate the annual percentage change (APC) and the average annual percentage change (AAPC). In addition, the age-period-cohort (APC) model was employed to explore the effects of age, period, and cohort on CRC mortality. The autoregressive integrated moving average (ARIMA) model was utilized to predict the disease burden in 2022–2036. We also compared the CRC burden attributed to high red meat in China with 204 countries worldwide. Results: The results showed that the number of CRC deaths in China due to high red meat consumption increased nearly 2.5 times, from 17,608 (95% UI: -3 to 36,613) in 1990 to 43,580 (95% UI: -16 to 92,083) in 2021. Male CRC deaths exhibited a more pronounced increase, rising from 9,800 in 1990 to 27,600 in 2021. Additionally, the number of DALYs increased from 518,213 (95% UI: -105,107 to 1,074,174) in 1990 to 1,091,788 (95% UI: -509 to 2,295,779) in 2021. Joinpoint regression analysis confirmed that the AAPC in ASDR and ASMR was − 0.20 (95% CI: -0.40 ∼ 0.00) and − 0.30 (95% CI: -0.40 ~ -0.10). When age, period, and cohort effects were examined as the reference group, the risk of CRC was found to increase with age. However, women experienced a marked decline in both period and cohort effects compared to men. Conclusions: Compared to global levels, the burden in China is heavier. In terms of mortality or DALY standardized rates, Chinese women show a similar downward trend to the overall trend, while Chinese men show a striking upward trend. This study provides valuable insights into enhancing CRC prevention and improving dietary patterns in China. [ABSTRACT FROM AUTHOR]

Background: Employees at the Ihlenberg toxic waste landfill in northern Germany were found to have an increased risk of cancer and cancer-related deaths in previous analyses covering the time period from 1983 to 2008. The present study aimed to quantify cancer risk and all-cause mortality in the employee cohort in 2009 to 2021. Methods: In this retrospective cohort study, cancers were identified by linkage with cancer registries, and employee deaths were obtained from population registries. Standardized incidence ratios (SIRs) for cancers and standardized mortality ratios (SMRs) were calculated to quantify cancer and mortality risk in the employee cohort. The effects of employment duration and different latency periods up to 30 years were additionally considered. Results: The cohort of 590 employees (432 men, 158 women) who worked at the landfill for at least 3 months between 1983 and 2018 was established from human resource management documentation and followed from January 1, 2009 until December 31, 2021. During this follow-up period, the SIR for all cancers combined was 0.69 (95% confidence interval (CI): 0.47, 0.98) and the SMR for all-cause mortality was 0.51 (95% CI: 0.35, 0.73). Longer employment at the landfill was not associated with increased cancer incidence or mortality. Conclusions: Employment at the landfill, expected to reflect occupational exposure to toxic waste, was not associated with increased cancer incidence or mortality in the employee cohort. Preventive measures to reduce exposure and to promote a healthy lifestyle should be maintained at the landfill. [ABSTRACT FROM AUTHOR]

Background: Patients with arthritis exhibit abnormal serum folate concentrations and have a higher incidence of cancer. The aim of this study was to investigate the association of serum folate concentrations with cancer mortality among individuals with arthritis. Methods: This cohort study included 7,514 patients with arthritis from National Health and Nutrition Examination Survey (NHANES) 1999 to 2016 and NHANES III (1988–1994). Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Serum folate concentrations were categorized into 4 groups, group 1 (≤ 17 nmol/L); group 2 (17-≤34 nmol/L); group 3 (34-≤51 nmol/L); and group 4 (> 51 nmol/L). Cox regression models were used to calculate hazard ratios and 95% confidence intervals for the associations between folate concentrations and the risk of mortality. Results: During a median follow-up of 9.75 [interquartile range, IQR, 5.75–14.5] years, there were 2,602 all-cause deaths, 949 deaths due to cardiovascular disease, and 478 deaths due to cancer. A non-linear association was observed for folate concentrations with the risk of cancer mortality (P < 0.001) among arthritis patients. Compared with the reference group 2, the hazard ratios for cancer mortality were 1.75 (95% CI, 1.15–2.69) in group 1, 1.70 (95% CI, 1.17–2.46) in group 3, and 1.60 (95% CI, 1.13–2.25) in group 4. Conclusions: This study shows that both low and high levels of serum folate are associated with an increased risk of cancer mortality among individuals with arthritis, indicating a potential beneficial role of maintaining moderate serum folate concentrations in decreasing the risk of cancer mortality among this population. [ABSTRACT FROM AUTHOR]

Background: This paper identifies differences in all-cancer incidence and mortality between Pakistani-born (PB), Bangladeshi-born (BB), their descendants, and the White British (WB) in England and Wales. Pakistanis and Bangladeshis are the most marginalised and disadvantaged groups in England and Wales yet, are found to have low cancer mortality and low all-cause mortality. Previous studies though have not looked at generational differences, applied individual-level data nor separated Pakistanis and Bangladeshis from each other and other Asian groups. Methods: We use the Office for National Statistics Longitudinal Study of England and Wales which is a 1% representative sample of the population. We apply event history analysis on a study period from 1971 to 2016, following individuals from age 20 until a first cancer incidence, censoring at emigration or death. We observe 10,885,500 person-years and 71,926 cancer incidences for WB; 125,700 person-years and 295 events for PB; 53,900 person-years and 113 events for BB and 26,900 person-years and 24 events for descendants. Following incidence, we study a maximum of ten years until a death from cancer, or censoring. In this second analysis on mortality our sample has 329,700 person-years and 31,689 cancer deaths for WB; 1,200 person-years and 104 events for PB; 400 person-years and 50 events for BB and 100 person-years and 10 events for descendants. Results: Results from the fully adjusted models show that the risk of cancer incidence is lower for PB, BB and descendants compared to the WB native group. Estimated hazard ratio (HR) equals 0.42 for PB (95% confidence interval (CI): 0.38–0.47), for BB HR is 0.38 (CI: 0.32–0.46) and, for descendants HR is 0.36 (CI: 0.24–0.54). Results for cancer mortality after incidence show HR for PB is 0.93 (CI: 0.76–1.12), for BB it is 0.95 (CI: 0.72–1.25) and for descendants HR equals 1.62 (CI: 0.87–3.02 - significant at 90%). Conclusions: Using high quality representative data, we show that lower incidence of cancer and not better survival is the driver of the low cancer mortality previously found. This advantage persists across immigrant generations, but all-cancer mortality following incidence may be elevated for descendants. [ABSTRACT FROM AUTHOR]

Objective: This systematic review update synthesized recent evidence on the benefits and harms of breast cancer screening in women aged ≥ 40 years and aims to inform the Canadian Task Force on Preventive Health Care's (CTFPHC) guideline update. Methods: We searched Ovid MEDLINE® ALL, Embase Classic + Embase and Cochrane Central Register of Controlled Trials to update our searches to July 8, 2023. Search results for observational studies were limited to publication dates from 2014 to capture more relevant studies. Screening was performed independently and in duplicate by the review team. To expedite the screening process, machine learning was used to prioritize relevant references. Critical health outcomes, as outlined by the CTFPHC, included breast cancer and all-cause mortality, treatment-related morbidity and overdiagnosis. Randomized controlled trials (RCTs), non/quasi RCTs and observational studies were included. Data extraction and quality assessment were performed by one reviewer and verified by another. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool for RCTs and the Joanna Brigg's Institute (JBI) checklists for non-randomized and observational studies. When deemed appropriate, studies were pooled via random-effects models. The overall certainty of the evidence was assessed following GRADE guidance. Results: Three new papers reporting on existing RCT trial data and 26 observational studies were included. No new RCTs were identified in this update. No study reported results by ethnicity, race, proportion of study population with dense breasts, or socioeconomic status. For breast cancer mortality, RCT data from the prior review reported a significant relative reduction in the risk of breast cancer mortality with screening mammography for a general population of 15% (RR 0.85 95% CI 0.78 to 0.93). In this review update, the breast cancer mortality relative risk reduction based on RCT data remained the same, and absolute effects by age decade over 10 years were 0.27 fewer deaths per 1000 in those aged 40 to 49; 0.50 fewer deaths per 1000 in those aged 50 to 59; 0.65 fewer deaths per 1000 in those aged 60 to 69; and 0.92 fewer deaths per 1000 in those aged 70 to 74. For observational data, the relative mortality risk reduction ranged from 29 to 62%. Absolute effects from breast cancer mortality over 10 years ranged from 0.79 to 0.94 fewer deaths per 1000 in those aged 40 to 49; 1.45 to 1.72 fewer deaths per 1000 in those aged 50 to 59; 1.89 to 2.24 fewer deaths per 1000 in those aged 60 to 69; and 2.68 to 3.17 fewer deaths per 1000 in those aged 70 to 74. For all-cause mortality, RCT data from the prior review reported a non-significant relative reduction in the risk of all-cause mortality of screening mammography for a general population of 1% (RR 0.99, 95% CI 0.98 to 1.00). In this review update, the absolute effects for all-cause mortality over 10 years by age decade were 0.13 fewer deaths per 1000 in those aged 40 to 49; 0.31 fewer deaths per 1000 in those aged 50 to 59; 0.71 fewer deaths per 1000 in those aged 60 to 69; and 1.41 fewer deaths per 1000 in those aged 70 to 74. No observational data were found for all-cause mortality. For overdiagnosis, this review update found the absolute effects for RCT data (range of follow-up between 9 and 15 years) to be 1.95 more invasive and in situ cancers per 1000, or 1 more invasive cancer per 1000, for those aged 40 to 49 and 1.93 more invasive and in situ cancers per 1000, or 1.18 more invasive cancers per 1000, for those aged 50 to 59. A sensitivity analysis removing high risk of bias studies found 1.57 more invasive and in situ cancers, or 0.49 more invasive cancers, per 1000 for those aged 40 to 49 and 3.95 more invasive and in situ cancers per 1000, or 2.81 more invasive cancers per 1000, in those aged 50 to 59. For observational data, one report (follow-up for 13 years) found 0.34 more invasive and in situ cancers per 1000 in those aged 50 to 69. Overall, the GRADE certainty of evidence was assessed as low or very low, suggesting that the evidence is very uncertain about the effect of screening for breast cancer on the outcomes evaluated in this review. Conclusions: This systematic review update did not identify any new trials comparing breast cancer screening to no screening. Although 26 new observational studies were identified, the overall quality of evidence remains generally low or very low. Future research initiatives should prioritize studying screening in higher risk populations such as those from different ages, racial or ethnic groups, with dense breasts or family history. Systematic review registration: Protocol available on the Open Science Framework: https://osf.io/xngsu/ [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the leading cause of cancer-related mortality among women globally, affecting approximately one-quarter of all female cancer patients and accounting for one-sixth of cancer-related deaths in women. Despite significant advancements in diagnostic and therapeutic approaches, breast cancer treatment remains challenging due to issues such as recurrence and metastasis. Recently, a novel form of regulated cell death, termed cuproptosis, has been identified. This process disrupts mitochondrial respiration by targeting the copper-dependent cellular pathways. The role of cuproptosis has been extensively investigated in various therapeutic contexts, including chemotherapy, immunotherapy, radiotherapy, and nanotherapy, with the development of novel drugs significantly improving clinical outcomes. This article aims to further elucidate the connection between cuproptosis and breast cancer, focusing on its therapeutic targets, signaling pathways, and potential biomarkers that could enhance treatment strategies. These insights may offer new opportunities for improved patient care and outcomes in breast cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Cancer is a major cause of mortality worldwide, and differences in cancer mortality rates between countries are, in part, due to differences in access to cancer care, including medicines. National essential medicines lists (NEMLs) play a role in prioritization of healthcare expenditure and access to medicines. We examined the association between amenable cancer mortality and listing medicines used in the management of eight cancers (non-melanoma skin, uterine, breast, Hodgkin lymphoma, colon, leukemia, cervical, and testicular) in national essential medicines lists of 158 countries and summarized changes to the inclusion of cancer treatments in NEMLs. Methods: We conducted a cross-sectional examination of NEMLs for 158 countries, which were obtained in May 2023. We identified medicines used to treat each of the eight cancers and determined the number of medicines listed by NEMLs for each cancer. We conducted multiple linear regressions to examine the association between the number of medicines listed on the NEMLs and cancer mortality. Results: We found associations between cancer medicine listing and outcomes for six of the eight examined cancers (non-melanoma skin cancer (p = 0.001), uterine cancer (p = 0.006), breast cancer (p = 0.001), Hodgkin lymphoma (p = 0.021), colon cancer (p = 0.006), and leukemia (p = 0.002)), when adjusting for healthcare expenditure and population size. Conclusion: There was an association between listing cancer medicines on NEMLs and cancer mortality. Further research is required to explore how cancer mortality may be impacted by other cancer interventions, as well as policies to improve equitable access to cancer care. [ABSTRACT FROM AUTHOR]

Background: The CALLY index, which is derived from C-reactive protein (CRP) content, serum albumin level, and total lymphocyte count, reflects the immune, nutritional, and inflammatory status of the body. Lack of sufficient evidence on the correlation between the CALLY index and the prognosis of cancer patients with various cancer forms. This study seeks to elucidate the association between the CALLY index and mortality from all causes as well as specific causes in cancer patients within a U.S. population. Methods: This investigation encompassed 3511 cancer-afflicted adults from the National Health and Nutritional Examination Surveys (NHANES) spanning 1999 to 2018. The CALLY index was measured at baseline only. The relationship between the CALLY index and mortality from both all causes and cancer specifically was examined using Cox proportional hazards models. Additionally, restricted cubic spline, piecewise linear regression, and various subgroup and sensitivity analyses were employed. Results: Over a median follow-up of 103 months, 1,355 deaths occurred, and the incidence of all-cause mortality for these participants was 38.34%. Our findings indicate that an elevated CALLY index correlates with a diminished risk of all-cause mortality. Upon applying a natural logarithmic transformation to the CALLY index, the comprehensively adjusted model revealed that each one-unit increment in ln CALLY corresponded to a 18% decrease in all-cause mortality risk among cancer patients (HR = 0.82, 95% CI:0.79–0.86). Analyses of mortality due to cardiac and cancer-related causes yielded consistent results, which were robust across various subgroup and sensitivity analyses. Conclusion: The CALLY index demonstrated a linear and negative association with all-cause mortality, as well as mortality caused by cancer and cardiac conditions, highlighting its significant prognostic value in patients with oncological conditions. [ABSTRACT FROM AUTHOR]

Background: Disparities in breast cancer mortality persist despite improvements in screening and therapeutic options. Understanding the impact of social determinants of health on disparate breast cancer outcomes is challenging due to heterogeneity of prior assessments. We examined the association between social vulnerability and breast cancer stage at diagnosis and mortality using a standardized measure of population risk for external stressors on health. Methods: Using institutional cancer registry data, female patients aged 18 or older diagnosed with breast cancer between 2012 and 2019 were assigned a 2018 Social Vulnerability Index (SVI) rank based upon home address census tract. We used multinomial logistic regression and Cox proportional hazards model to examine the relationships between SVI and breast cancer stage at diagnosis and all-cause mortality. Covariates included age and, when assessing mortality, cancer stage, comorbidities, body mass index, insurance type, and treatment regimen. Results: A total of 3,499 women with a median age of 59 (IQR 48–69) were included. 60% were White and 31% were Black. Median SVI was 0.36 (IQR 0.14–0.68) and median follow-up was 58 months (IQR 37.3–83.9). On adjusted analyses, each decile increase in SVI resulted in an 11% (OR 1.11, 95% CI 1.06–1.16, p <.001) and 15% (OR 1.15, 95% CI 1.09–1.21, p <.001) greater odds of presenting with Stage III or IV breast cancer, respectively, compared to DCIS. For patients who underwent surgery (N = 2916), each decile increase in SVI was associated with a 6% increase in all-cause mortality risk (HR 1.06, 95% CI 1.01–1.12, p =.01). Mortality risk was 1.5 times (HR 1.52, 95% CI 1.02–2.26, p =.04) greater for those in the most vulnerable quartile compared to the least vulnerable quartile. Conclusions: Women living in socially vulnerable communities presented with more advanced breast cancers and suffered worse survival. The SVI can be used to identify patients at risk for delayed cancer presentation and increased mortality. This tool can inform geographically targeted resource allocation and interventions aimed at reducing breast cancer care disparities. [ABSTRACT FROM AUTHOR]

Introduction: Gastrointestinal cancers encompass malignant tumors of multiple digestive system organs in humans. Each type of digestive system cancer also contains different histological types, each of which has a distinct prognosis. The survival time of cancer patients has significantly extended with the development of modern medicine, allowing for primary cancers occurring more than once in a lifetime. Methods: The study analyzed multiple primary gastrointestinal cancers, including esophagus, stomach, liver, gallbladder, small bowel, colon, rectum, and anus, based on the Surveillance, Epidemiology, and End Results (SEER) database from 2016 to 2019 in the United States. A total of 119,760 cases were included in this study. Each gastrointestinal cancer was analyzed separately based on the International Classification of Diseases for Oncology third edition (ICD-O-3) for the common histologic type. Meanwhile, based on the sequence of cancer occurrence in the patients, they were divided into the one primary (OP) group and the multiple primaries (MP) group. The multiple primaries group was further subdivided into the first of multiple primaries (FMP) group and the non-first of multiple primaries (NFMP) group. The Kaplan-Meier method with the log-rank test was used to analyze overall survival (OS), while the Cox regression model was used for univariate and multivariate analyses. Results: The study enrolled nine organs of the digestive system and twenty histologic types of primary gastrointestinal cancers. The characteristics of patients in different groups with various cancers, overall survival of these patients, and the risk factors for developing these cancers were comprehensively analyzed. The comprehensive analysis revealed the connection between the occurrence sequence of cancers and different outcomes for patients. Conclusions: Different prognoses were observed in patients with different sequences of various primary gastrointestinal cancers. Patients with high mortality cancers in the FMP group may have potential factors, such as high treatment sensitivity, that could lead to improved OS. Patients with low mortality cancers in the NFMP group could benefit from positive treatment therapies. [ABSTRACT FROM AUTHOR]

Background: Cancer survivors face many challenges in long-term health management, including malnutrition, systemic inflammation, and sleep issues, which significantly affect their survival and quality of life. Methods: A prospective cohort study was derived from the National Health and Nutrition Examination Survey from 2005–2018 harboring 1,908 cancer survivors (weighted population, 11,453,293), of whom 688 deaths (220 from cancer mortality, 468 from non-cancer mortality). The Advanced Lung Cancer Inflammation Index (ALI) was used as a measure of nutritional status and systemic inflammation in cancer patients. Weighted multivariable Cox proportional hazards regression models were utilized to explore the independent and combined effects of ALI and sleep quality on mortality outcomes. Results: The participants with a high ALI were more likely to be female, aged 40 to 64 years, non-Hispanic white, and have a higher BMI. We observed that elevated ALI levels were associated with decreased risks of all-cause mortality (Hazard ratio [HR] = 0.601, 95% Confidence interval [CI] = 0.521–0.695, P < 0.001), cancer-specific mortality (HR = 0.659, 95% CI = 0.497–0.870, P = 3.34 × 10–3) and non-cancer-specific mortality (HR = 0.579, 95% CI = 0.478–0.701, P < 0.001). Similarly, better sleep quality (e.g., without sleep troubles) was associated with lower risks of all-cause mortality (HR = 0.761, 95% CI = 0.620–0.933, P = 8.79 × 10–3) and non-cancer-specific mortality (HR = 0.713, 95% CI = 0.572–0.890, P = 2.80 × 10–3). Notably, the joint analysis showed that cancer survivors with higher ALI levels and better sleep quality (e.g., standard sleep duration) had the lowest risks of all-cause (HR = 0.468, 95% CI = 0.352–0.622, P < 0.001), cancer-specific mortality (HR = 0.631, 95% CI = 0.333–0.672, P = 7.59 × 10–3) and non-cancer-specific mortality (HR = 0.440, 95% CI = 0.315–0.615, P < 0.001). Conclusions: This study suggests that better nutritional and inflammatory status, combined with good sleep quality, may contribute to improved survival among cancer survivors. These results underscore the potential clinical importance of integrating nutritional and sleep quality assessments into the long-term care of cancer survivors to enhance their overall prognosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of serum creatinine-cystatin C ratio (Cr/CysC) with long-term all-cause mortality and cause-specific (cardiovascular and cancer) mortality among US general adults. Methods: This nationally representative cohort study included adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. Participants were linked to National Death Index data from the survey date through December 31, 2019. Weighted Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals (CIs), and restricted cubic splines and stratified analyses were also performed. Results: A total of 12,914 participants were included in this study (mean [SD] age, 45.3 [17.3] years; males, 48.9%). During a median follow-up of 17.9 years (maximum follow-up, 20.8 years), 3439 total deaths occurred, including 1098 cardiovascular deaths and 736 cancer deaths. Cumulative incidence curves revealed that increased Cr/CysC ratio had lower risk of all-cause (P < 0.001), cardiovascular (P < 0.001) and cancer (P < 0.001) mortality. Cox regression an Fine-Gray hazards models demonstrated that the multivariable-adjusted hazard ratios comparing the highest vs. lowest quartile of Cr/CysC ratio were 0.40 (95% CI, 0.34–0.47; P < 0.001) for all-cause mortality, 0.68 (95% CI, 0.52–0.88; P < 0.001) for cardiovascular mortality, and 0.51 (95% CI, 0.36–0.71; P < 0.001) for cancer mortality. Nonlinear association was observed for Cr/CysC ratio and all-cause mortality (P = 0.018 for nonlinearity), and linear associations were observed for Cr/CysC ratio and cardiovascular (P = 0.212 for nonlinearity) and cancer (P = 0.550 for nonlinearity) mortality. Besides, a series of sensitivity analyses ensured the robustness of the results. Conclusions: In this cohort of US adults, Cr/CysC ratio was negatively associated with all-cause, cardiovascular, and cancer mortality. Our study suggests that Cr/CysC ratio may serve as a simple and effective predictor of long-term health outcomes. [ABSTRACT FROM AUTHOR]

Background: Colon adenocarcinoma (COAD) ranks as the third most prevalent and lethal cancer in 2020, with metastasis being the primary cause of cancer-related mortality. A comprehensive understanding of the mechanism underlying distant metastasis is imperative for enhancing the prognosis and quality of life of patients with COAD. Methods: This study employed gene set enrichment analysis (GSEA) on RNA-sequencing data from 408 patients with COAD in The Cancer Genome Atlas (TCGA) database. GSEA analysis was applied to find the significant hallmark gene set, and genes in the significant hallmark gene set was performed by univariate Cox regression to select the key gene. Then, multivariate Cox regression model was constructed. And various databases were utilized to validate and find the significant oncoprotein and hallmark gene set of the key gene. In addition, the expression of key regulators in para-carcinoma tissue, colon cancer and distant metastases samples were detected by real-time PCR, Immunohistochemistry and Western blot. Additionally, the biological functions were examined by in vitro and in vivo experiments. The scRNA-seq and CellphoneDB were performed to explore cell characters in COAD and the potential mechanism of metastasis. Results: The regulatory network analysis revealed SRC/YAP1 as the most significant oncoprotein and signature gene set associated with SNTB1. Moreover, significant SNTB1 overexpression in COAD metastatic tissues was observed compared to para-carcinoma and primary COAD tissues. Co-immunoprecipitation assays demonstrated the formation of a complex between SNTB1 and SRC proteins. Furthermore, the overexpression of SNTB1 enhanced the proliferation, migration and invasion capacities of COAD cell lines. Caudal vein injection of COAD cells overexpressing SNTB1 in nude mice resulted in increased tumour growth and metastasis to the lung, liver and bone. Finally, single cell RNA-seq revealed alterations in the cellular subtypes of COAD, and CellphoneDB indicated that the interaction between cancer cells exhibiting high SNTB1 expression and enterocytes promoted EMT through cellular communications involving TGF-β, accelerating metastasis in COAD. Conclusion: This study postulates that SNTB1 interacts with SRC to activate the Hippo-YAP pathway, thereby promoting COAD metastasis. Furthermore, cellular communication with enterocytes promotes EMT, facilitating metastasis. These findings propose novel therapeutic targets for preventing or treating metastatic COAD. [ABSTRACT FROM AUTHOR]

Background: The relationship between serum urea concentration and cancer in patients with metabolic syndrome (MetS) remains unclear. This study aimed to investigate the association between serum urea concentration and 16 site-specific cancers, overall cancer incidence, and cancer mortality in individuals with MetS. Methods: We analysed the data of 108,284 individuals with MetS obtained from the UK Biobank. The Cox proportional hazards model was used to determine the association between serum urea concentration at recruitment and cancer. The Benjamini–Hochberg correction was used to account for multiple comparisons. Results: Over the median follow-up period of 11.86 years, 18,548 new incident cases of cancer were documented. There were inverse associations of urea concentration with overall cancer incidence, and the incidence of oesophageal and lung cancers, with respective hazard ratios (95% confidence intervals) [HR (95% CI)] for the highest (Q4) vs lowest (Q1) urea quartiles of 0.95 (0.91–0.99), 0.68 (0.50–0.92), and 0.76 (0.64–0.90). However, high serum urea concentrations increased the male prostate cancer risk (HR 1.15; 95% CI 1.02–1.30). Although the Cox model indicated a protective effect of higher urea levels against stomach (HR 0.67; 95% CI 0.45–0.98; p = 0.040; FDR 0.120) and colorectal cancer (HR 0.86; 95% CI 0.74–0.99; p = 0.048; FDR 0.123), no strong evidence of association was found after applying the Benjamin-Hochberg correction. Moreover, across the median follow-up period of 13.77 years for cancer mortality outcome, 5034 cancer deaths were detected. An "L-shaped" nonlinear dose–response relationship between urea concentration and cancer mortality was discovered (p-nonlinear < 0.001), and the HR (95% CI) for urea concentration Q4 vs Q1 was 0.83 (0.77–0.91). Conclusions: Serum urea concentration can be considered as a valuable biomarker for evaluating cancer risk in individuals with MetS, potentially contributing to personalised cancer screening and management strategies. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, highlighting the necessity for multifaceted treatment strategies, including preoperative treatment (PT), which can enhance surgical outcomes and provide prognostic insights. This study aims to clarify the impact of PT-induced changes in mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) expression, potentially informing tailored treatment strategies and improving clinical outcomes for CRC patients. Methods: This retrospective study analyzed 120 paired samples from CRC patients who underwent preoperative treatment, comparing pre- and post-treatment specimens. A control group of 60 untreated surgical specimens was also included. Immunohistochemistry assessed MMR proteins (MSH6, MSH2, MLH1, PMS2) and HER2 expression. MSI status was determined in samples with low MMR expression. Results: Compared to pre-treatment samples, post-treatment samples exhibited lower levels of MSH6, MSH2, and total MMR expression, along with higher levels of HER2 expression. However, when compared to the untreated control group, there were no significant differences in the expression of MSH6, total MMR, and HER2. All samples that exhibited weak MMR expression and those that shifted to deficient mismatch repair (dMMR) status following treatment had stable microsatellite status. No clear clinicopathological characteristics or prognostic factors were found to be associated with changes in MMR and HER2 expression, except for the use of fluorouracil or capecitabine, which was related to changes in total MMR scores. ypTNM stage and TRG scores were identified as independent factors affecting disease progression in our study. Conclusions: PT is associated with a reduction in MMR expression, notably for the MSH2 protein, while it does not appear to influence HER2 expression. [ABSTRACT FROM AUTHOR]

Background: Gallbladder cancer is a major health concern in China, and awareness of the associated incidence and mortality rates is particularly important given the aging population. Objective: To determine trends in gallbladder cancer incidence and mortality rates over 12 years and quantitatively analyze the influence of demographic factors on these rates in China. Methods: We performed a retrospective study of 98,860 Chinese citizens using the Chinese Cancer Registry, a national database. Gallbladder cancer incidence and mortality data pertaining to patients treated between 2005 and 2017 were collected. Joinpoint regression models were used to estimate the annual percentage change (APC) and average APC (AAPC). We used age-period-cohort analyses and decomposition methods to investigate differing trends in incidence and mortality. Results: The age-standardized gallbladder cancer incidence and mortality rates in China trended downward between 2005 and 2017, with AAPCs of -2.023% and -1.603%, respectively. Coefficients of age effect for incidence rate increased with age up to 70 years and peaked at 70–79 years, while coefficients of age effect for the mortality rate showed a consistent increase with age. Both coefficients of period for incidence and mortality rates increased in more recent periods; in terms of the cohort effect, coefficients of cohort for rates generally decreased in later birth years but showed a partial rise between 1982 and 1996. The crude incidence rates of gallbladder cancer according to demographic and non-demographic factors were 626.09% and -526.09% respectively (366.23% and -266.23% among men, and 6068.93% and -5968.93% among women, respectively). The rates were 543.01% and -443.01%, respectively, in urban areas and were 68.22% and 31.78%, respectively, in rural areas. The mortality rates according to demographic and non-demographic factors were -495.93% and 595.93%, respectively (-1763.10% and -1863.10% for men and -270.56% and -370.56% for women, respectively). These rates were -930.33% and 1030.33%, respectively, in urban areas and were 101.48% and -1.48%, respectively, in rural areas. Conclusions: The overall standardized gallbladder cancer incidence and mortality rates in China are trending downward, but not sufficiently so. Proper living and eating habits should be encouraged while exploring the establishment of long-term, standardized gallbladder cancer screening programs. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most prevalent cancer worldwide. Belgium shows high age-standardized incidence rates, but also high survival rates. Like many health outcomes, breast cancer has been associated with multiple factors of socioeconomic status. This paper aims to (a) map educational differences in breast cancer incidence, mortality and death rates within 5 years of diagnosis, (b) update earlier trends in breast cancer mortality rates in Belgium for the 2004–2013 period and (c) investigate the role of fertility indicators as mediating factors in the association between education and breast cancer outcomes. Methods: Data consisted of a linkage between the 2001 Belgian Census, register data on mortality and cancer incidence data (2004–2013) from the Belgian Cancer Registry. We calculated age standardized rates, rate ratios (Poisson regression) and hazard ratios (Cox regression) and furthermore also applied the method of Excess Portion Eliminated (EPE) in a mediation analysis of the fertility indicators. We stratified our analysis by age: younger than 50 (premenopausal) and 50 or older (postmenopausal). Results: We observed striking differences in breast cancer incidence, all-cause and cause-specific death rates 5-years after diagnosis by educational level. Higher educated women had higher breast cancer incidence, but also lower all-cause and lower cause-specific death rates; adding up to zero differences in breast cancer mortality in the postmenopausal group and lower breast cancer mortality in the premenopausal group. Conclusion: A notable shift in the social gradient occurred since the 1990's, favouring higher-educated women in recent years. Especially, with regards to survival after diagnosis there is potential for policy intervention. Stage at diagnosis played a crucial role, but differences between socioeconomic groups remained significant after including this parameter. While fertility indicators played a role, the impact was less pronounced than expected. [ABSTRACT FROM AUTHOR]

Lung cancer leads in causing cancer-related mortality worldwide, continually posing a significant threat to human health. Current imaging diagnostic techniques, while offering non-invasive detection, suffer from issues such as insufficient sensitivity and the risks associated with radiation exposure. Pathological diagnosis, the gold standard for confirmation, also faces challenges like invasiveness and high costs. In treatment, surgery, radiotherapy, and chemotherapy are the main modalities, each encountering challenges related to precision, environmental adaptability, and side effects. Nanotechnology's advancement provides new solutions for the diagnosis and treatment of lung cancer, promising to enhance diagnostic accuracy and reduce side effects during treatment. This article introduces the main types of nanomaterials used in the field of lung cancer, offering a comprehensive overview of current research on the application of nanotechnology in early screening, diagnosis, treatment, and monitoring of lung cancer, and summarizing ongoing clinical research findings. [ABSTRACT FROM AUTHOR]

Background: The efficacy of lung cancer screening (LCS) to reduce lung cancer specific mortality is heavily dependent on adherence to recommended screening guidelines, with real-world adherence rates reported to be drastically lower than rates described in clinical trials. There is a dearth in the literature on reminder processes and clinical workflows used to address adherence and robust data is needed to fully understand which clinical set-ups, processes, and context enhance and increase continued LCS participation. This paper describes a protocol for an environmental scan of adherence and reminder processes that are currently used in LCS programs across the United States. Methods: This study will triangulate data using a 3-step explanatory sequential mixed methods design to describe mechanisms of current adherence and reminder systems within academic and community LCS programs to pinpoint clinic or system barrier and facilitator combinations that contribute to increased adherence. In step 1, surveys from a nationally representative sample of LCS programs will yield quantitative data about program structure, volume, and tracking/reminder processes and messages. After completion of the survey, interested LCS program personnel will be invited to participate in an in-depth interview (step 2) to explore current processes and interventions used for adherence at the participant and program level. Finally, in step 3, triangulation of quantitative and qualitative data will be completed through qualitative comparative analysis to identify combinations of components that affect higher or lower adherence. Discussion: This research advances the state of the science by filling a gap in knowledge about LCS program characteristics and processes associated with better adherence which can inform the development and implementation of interventions that are scalable and sustainable across a wide variety of clinical practice settings. [ABSTRACT FROM AUTHOR]

Background: Menopausal hormone therapy (MHT) is associated with an increased risk of postmenopausal breast cancer, predominantly the luminal A-like subtype. The impact of MHT on deaths from breast cancer subtypes is less understood. This study aimed to explore associations between MHT use and the incidence, mortality, and survival of intrinsic-like breast cancer subtypes. Methods: Data from 160,881 participants with self-reported MHT use from the prospective Norwegian Women and Cancer Study were analyzed. Among them, 7,844 incident breast cancer cases, and 721 breast cancer-specific deaths occurred. Cox proportional hazard regression was performed to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between MHT use and the incidence, mortality, and survival of breast cancer subtypes. Results: MHT use was associated with increased risk of overall, luminal A-like, and luminal B-like breast cancer, with respective HRs of 1.44 (95% CI 1.36–1.52), 1.41 (95% CI 1.31–1.52), and 1.23 (95% CI 1.09–1.40) among current estrogen-progestin therapy (EPT) users compared with never users. The risk increased by 4%, 4%, and 2% per year of EPT use for overall, luminal A-like, and luminal B-like breast cancers, respectively. MHT use was also associated with increased risk of overall and luminal A-like breast cancer mortality, with HRs 1.61% (95% CI 1.36–1.91) and 2.15% (95% CI 1.51–3.05) increased risk among current EPT users compared with non-users. Among patients with breast cancer, pre-diagnostic MHT use was not associated with worse survival from overall breast cancer but was inversely associated with survival from triple-negative breast cancer (TNBC; HR death 0.41; 95% CI 0.24–0.73 among current users). Results varied significantly according to tumor subtype (pheterogeneity = 0.02). Conclusions: Our study suggests that MHT use increases the risk of incident and fatal overall and luminal A-like, and incident luminal B-like breast cancer but does not decrease overall survival among patients with breast cancer. Further research is needed to elucidate the mechanisms underlying MHT use and breast cancer lethality, and to explore whether MHT use among patients with TNBC is indeed free from harm. [ABSTRACT FROM AUTHOR]

Background: Unfavorable social determinants of health (SDoH) are associated with depression. Both depression and SDoH are associated with increased risks of mortality, but their joint impacts on mortality risks remain unclear. This study aims to investigate the joint effects of depression and SDoH on mortality risk. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018, 24,727 adults aged ≥ 20 were included. SDoH was assessed based on the 5 domains outlined in the U.S. Healthy People 2030 initiative. The cumulative number of unfavorable SDoH was calculated and categorized into low and high burden levels. The definition of depression was based on the Patient Health Questionnaire-9 (PHQ-9) scores ≥ 10. The joint associations of depression and SDoH with all-cause, cardiovascular disease (CVD), and cancer mortality were examined using Cox proportional hazard models. Results: We identified 2,377 (6.84%) all-cause deaths (CVD, 717; cancer, 606) during a median follow-up of 7.0 years. Depression was associated with increased mortality risks, and SDoH could explain 32.4% and 28.3% of the associations between depression and all-cause and CVD mortality, respectively. No significant interactions were observed between depression and SDoH on mortality. However, a low burden of unfavorable SDoH reduced the risk of all-cause mortality in depressed patients (hazard ratio [HR], 0.58; 95% confidence interval [CI]: 0.36–0.92). In the joint analysis, individuals with both depression and a high burden of unfavorable SDoH had the highest risks of all-cause and CVD mortality. Specifically, compared with individuals with no depression and a low burden of unfavorable SDoH, those with depression and a high burden of unfavorable SDoH had higher risks of all-cause (HR, 2.52; 95% CI: 2.01–3.18) and CVD mortality (HR, 2.79; 95% CI: 1.95–3.99). Conclusion: Adults with both depression and a high burden of unfavorable SDoH had the highest risks of all-cause mortality and CVD mortality. The result suggests considering depression and SDoH jointly in developing targeted intervention strategies to improve survival outcomes and calls for larger cohort studies and clinical trials to validate our findings. [ABSTRACT FROM AUTHOR]

Background: The effect of supplements on mortality risk in patients with cancer remains uncertain and has scarcely been investigated in subgroups of patients with varying characteristics. This study aimed to investigate the association between two popular supplements, fish oil and glucosamine, and mortality risk in a large population-based cohort and determine whether cardiovascular health and clinical prognosis influence these associations. Methods: This prospective cohort study analyzed the data of UK Biobank participants who were diagnosed with cancer. The associations of fish oil and glucosamine consumption with mortality were analyzed using Cox proportional hazards models. Subgroup analyses were performed to assess the effects of Life Essential 8 [LE8] scores (a measure of cardiovascular health) and cancer prognosis (grouped according to the survival rates of specific cancer types) on the associations between supplement use and mortality. Results: This analysis included 14,920 participants (mean age = 59.9 years; 60.2% female). One third (34.1%) of the participants reported using fish oil, and one fifth (20.5%) reported using glucosamine. Over a median follow-up of 12.0 years, 2,708 all-cause deaths were registered. The use of fish oil was associated with reduced risks of all-cause mortality (adjusted hazard ratio [aHR] = 0.89, 95% Confidence Interval [CI] = 0.81–0.97) and cancer mortality (aHR = 0.89, 95% CI = 0.81–0.98). Similarly, glucosamine use was associated with reduced risks of all-cause mortality (aHR = 0.83, 95% CI = 0.74–0.92) and cancer mortality (aHR = 0.83, 95% CI = 0.74–0.93) in the fully adjusted model. Subgroup analyses revealed that the protective effects of fish oil and glucosamine against mortality risk were only observed in patients with LE8 scores lower than the mean score or a poor cancer prognosis. Additionally, the association between glucosamine use and a reduced risk of CVD-related mortality was only observed in patients with lower LE8 scores. Conclusions: This large cohort study identified the potential differential impact of LE8 scores and cancer prognosis on the associations of fish oil and glucosamine supplementation with survival in patients with cancer. This suggests the importance of considering these factors in future research on supplements and in the provision of personalized integrative cancer care. [ABSTRACT FROM AUTHOR]

Background: Candidemia is an invasive mycosis with an increasing global incidence and high mortality rates in cancer patients. The production of biofilms by some strains of Candida constitutes a mechanism that limits the action of antifungal agents; however, there is limited and conflicting evidence about its role in the risk of death. This study aimed to determine whether biofilm formation is associated with mortality in cancer patients with candidemia. Methods: This retrospective cohort study included patients treated at Peru's oncologic reference center between June 2015 and October 2017. Data were collected by monitoring patients for 30 days from the diagnosis of candidemia until the date of death or hospital discharge. Statistical analyses evaluated the association between biofilm production determined by XTT reduction and mortality, adjusting for demographic, clinical, and microbiological factors assessed by the hospital routinary activities. Survival analysis and bivariate and multivariate Cox regression were used, estimating the hazard ratio (HR) as a measure of association with a significance level of p < 0.05. Results: A total of 140 patients with candidemia were included in the study. The high mortality observed on the first day of post-diagnosis follow-up (81.0%) among 21 patients who were not treated with either antifungal or antimicrobial drugs led to stratification of the analyses according to whether they received treatment. In untreated patients, there was a mortality gradient in patients infected with non-biofilm-forming strains vs. low/medium and high-level biofilm-forming strains (25.0%, 66.7% and 82.3%, respectively, p = 0.049). In treated patients, a high level of biofilm formation was associated with increased mortality (HR, 3.92; 95% p = 0.022), and this association persisted after adjusting for age, comorbidities, and hospital emergency admission (HR, 6.59; CI: 1.87–23.24, p = 0.003). Conclusions: The association between candidemia with in vitro biofilm formation and an increased risk of death consistently observed both in patients with and without treatment, provides another level of evidence for a possible causal association. The presence of comorbidities and the origin of the hospital emergency, which reflect the fragile clinical condition of the patients, and increasing age above 15 years were associated with a higher risk of death. [ABSTRACT FROM AUTHOR]

Background: The associations of weight change with all-cause and cause-specific mortality stratified by age remains unclear. We evaluated the age-stratified (< 65 vs ≥ 65 years) associations of weight change with all-cause and cause-specific mortality in a large sample of Chinese adults. Methods: Our cohort study included 746,991 adults aged at least 45 years from the Shenzhen Healthcare Big Data Cohort in China. BMI change were categorized as change within 5% (stable), decrease by 5% to 10%, decrease by > 10%, increase by 5% to 10%, and increase by > 10%. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, non-communicable disease, cardiovascular disease (CVD), and cancer mortality according to BMI change, with adjustment for potential confounders. Results: During a median follow-up of 2.2 years (2,330,180 person-years), there were 10,197 deaths. A notable interaction emerged between weight change and age. For participants ≥ 65 years, compared with stable BMI, more than a 10% decrease in BMI was associated with higher risk of all-cause mortality (HR: 1.69, 95% CI: 1.54–1.86), non-communicable disease mortality (HR: 1.67, 95% CI: 1.52–1.84), CVD mortality (HR: 1.55, 95% CI: 1.34–1.80), and cancer mortality (HR: 1.59, 95% CI: 1.33–1.92). Similar patterns of results for 5% to 10% decrease in BMI were observed. More than a 10% increase in BMI was associated with increased risk of all-cause mortality (HR: 1.13, 95% CI: 1.04–1.24), non-communicable disease mortality (HR: 1.14, 95% CI: 1.04–1.25), and CVD mortality (HR: 1.27, 95% CI: 1.12–1.44). For participants < 65 years, only more than a 10% decrease in BMI was associated with higher risk of all-cause mortality (HR: 1.41, 95% CI: 1.12–1.77), non-communicable disease mortality (HR: 1.43, 95% CI: 1.13–1.81), and cancer mortality (HR: 1.79, 95% CI: 1.29–2.47). Conclusions: Weight loss and excessive weight gain were associated with increased risks of mortality among older adults, while only excessive weight loss was associated with increased risks of mortality among middle-aged adults. [ABSTRACT FROM AUTHOR]

Background: Lung cancer remains a leading cause of cancer-related mortality worldwide. Autotransplantation has emerged as a potential surgical intervention in select cases, with the aim of achieving curative outcomes. This case report describes a novel approach combining lung autotransplantation with postoperative chemotherapy and immunotherapy, delineating the patient's journey over a period of three years. Case presentation: We report on a 37-year-old patient with stage IIIA non-small cell lung cancer (NSCLC) who underwent lung autotransplantation. Despite the complexity of the procedure, the patient had a favorable postoperative course. Adjuvant therapy included a PD-1 inhibitor and a standard chemotherapy regimen. The patient's follow-up involved regular clinical assessment, imaging, and functional status evaluation, demonstrating a remarkable disease-free survival at the three-year mark postoperatively. Conclusion: This case highlights the potential for lung autotransplantation coupled with immunotherapy and chemotherapy to yield significant long-term survival benefits in patients with NSCLC. The favorable outcome suggests that this integrative treatment strategy warrants further investigation and may offer hope to patients with similarly advanced lung cancer. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer (CC) is a serious public health concern, being the fourth most common cancer among women and a leading cause of cancer mortality. In Brazil, many women are diagnosed late, and in Mato Grosso, with its geographical diversity, there are specific challenges. This study analyzed hospital survival and its predictors using data from the Hospital Information System (SIH) of the Unified Health System (SUS) in Mato Grosso from 2011 to 2023. Methods: Cox regression and Kaplan-Meier models were applied to determine survival time and identify mortality predictors. The adjusted Hazard Ratio (AHR) with a 95% Confidence Interval (CI) was used to measure the association between the factors analyzed. Results: The hospital mortality rate was 9.88%. The median duration of hospitalization was 33 days (interquartile range [IQR]: 12–36), with a median survival of 43.7%. Patients were followed up for up to 70 days. In the multivariable Cox model, after adjusting for potential confounders, the risk of death during hospitalization was higher in patients aged 40–59 years (AHR = 1.39, p = 0.027) and 60–74 years (AHR = 1.54, p = 0.007), in the absence of surgical procedures (AHR = 4.48, p < 0.001), in patients with medium service complexity (AHR = 2.40, p = 0.037), and in the use of ICU (AHR = 4.97, p < 0.001). On the other hand, patients with hospital expenses above the median (152.971 USD) showed a reduced risk of death (AHR = 0.21, p < 0.001). Conclusion: This study highlights that hospitalized CC patients have reduced survival, underscoring the need for interventions to improve care, including strategies for early diagnosis and expanded access to adequately resourced health services. [ABSTRACT FROM AUTHOR]

Background: Urinary incontinence is frequent in the general population and affects men and women of all ages. UI carries an unsuspected load on the healthcare system. To investigate whether urinary incontinence is associated with all-cause, cardiovascular disease (CVD) and cancer mortality among US adults. Methods: The analyzed data was collected from the 2007–2016 National Health and Nutrition Examination Survey (NHANES) data. A total of 25,182 US participants with complete information about follow-up information and urinary incontinence (UI) were included in this cohort study. Univariate Cox regression analyses, the UpSet plot, multivariate Cox regression analysis, subgroup analysis of all-cause mortality, and Kaplan-Meier survival curve were employed to support the research objectives. Results: A total of 25,182 participants had a mean age of 49.8 ± 17.8 years, with 49.3% of them being male and 50.7% of them being female. In the unadjusted model, we found that the risk of all-cause mortality increased by 12% (95% CI 1.03–1.22, P = 0.008), the risk of CVD mortality increased by 21% (95% CI 1.07–1.36, P = 0.002), and the risk of Cancer mortality increased by 8% (95% CI 0.95–1.22, P = 0.243) among individuals with urinary incontinence. After adjusting for multiple variables, we found that the risk of all-cause mortality in patients with urinary incontinence decreased by 1% (95% CI 0.9–1.09), but this decrease was statistically insignificant (P = 0.868), and the risk of Cancer mortality decreased by 3% (95% CI 0.84–1.12, P = 0.686). The association between urinary incontinence and mortality risk were stable in stratified analyses. Conclusions: In our study, we found that urinary incontinence itself is an independent risk factor for death. The association between urinary incontinence and mortality became less significant after adjusting for covariates, this is a common occurrence in statistical analysis. Future research, with larger sample sizes and more robust study designs, is needed to further elucidate the complex relationship between urinary incontinence and mortality risk. [ABSTRACT FROM AUTHOR]

Background: Lung cancer, a leading global cause of cancer-related mortality, necessitates enhanced prognostic markers for improved treatment outcomes. We have previously shown a tumor suppressive role of cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1), which is targeted for degradation upon phosphorylation at S14 (pCASTOR1) in multiple types of cancer. This study focuses on the predictive value of pCASTOR1 in lung adenocarcinoma (LUAD) patients with KRAS mutations. Results: Employing a newly developed pCASTOR1 specific antibody, we found that tumor cells exhibited significantly elevated pCASTOR1 scores compared to non-tumor cells (P < 0.05). Higher pCASTOR1 scores predicted poorer overall survival (OS) (HR = 3.3, P = 0.0008) and relapse-free survival (RFS) (HR = 3.0, P = 0.0035) in male patients with KRAS mutations. pCASTOR1 remained an independent predictor for OS (HR = 4.1, P = 0.0047) and RFS (HR = 3.5, P = 0.0342) after controlling for other factors. Notably, in early-stage LUAD, elevated pCASTOR1 scores were associated with significantly worse OS (HR = 3.3, P = 0.0176) and RFS (HR = 3.1, P = 0.0277) in male patients with KRAS mutations, akin to late-stage patients. Conclusion: Elevated pCASTOR1 scores serve as biomarkers predicting poorer OS and RFS in male LUAD patients with KRAS mutations, offering potential clinical utility in optimizing treatment strategies for this subgroup. [ABSTRACT FROM AUTHOR]

Background: In the first year of the COVID-19 pandemic, data projections indicated an increase in cancer mortality for the following years due to the overload of health services and the replacement of health priorities. The first studies published with data from mortality records have not confirmed these projections. However, cancer mortality is not an outcome that occurs immediately, and analyses with more extended follow-up periods are necessary. This study aims to analyze the impact of the COVID-19 pandemic on the mortality from all types and the five most common types of cancer in Brazil and investigate the relationship between the density of hospital beds and mortality from COVID-19 in cancer patients in Brazil's Intermediate Geographic Regions (RGIs). Methods: The Brazilian Mortality Information System provided data on the deaths from trachea, bronchus, and lung, colorectal, stomach, female breast, and prostate cancer and all types of cancer, and from COVID-19 in individuals who had cancer as a contributing cause of death. Predicted rates for 2020–2022 were compared with the observed ones, through a rate ratio (RR). An association analysis, through multivariate linear regression, was carried out between mortality from COVID-19 in cancer patients, the rate of hospital beds per 100,000 inhabitants, and the Human Development Index of the 133 RGIs of Brazil. Results: In 2020, 2021, and 2022, mortality from all cancers in Brazil was lower than expected, with an RR of 0.95, 0.94, and 0.95, respectively, between the observed and predicted rates. Stomach cancer showed the largest difference between observed and expected rates: RR = 0.89 in 2020 and 2021; RR = 0.88 in 2022. Mortality from COVID-19 in cancer patients, which reached its peak in 2021 (6.0/100,000), was negatively associated with the density of hospital beds in the public health system. Conclusions: The lower-than-expected cancer mortality during 2020–2022 seems to be partly explained by mortality from COVID-19 in cancer patients, which was probably underestimated in Brazil. The findings suggested a protective role of the availability of hospital care concerning deaths due to COVID-19 in this population. More extensive follow-up is needed to understand the impact of the COVID-19 pandemic on cancer mortality. [ABSTRACT FROM AUTHOR]

Background: Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a significant cause of cancer-related mortality, with drug resistance posing a substantial obstacle to effective therapy. LncRNAs have emerged as pivotal regulators of NSCLC progression, suggesting potential targets for cancer diagnosis and treatment. Therefore, identifying new lncRNAs as therapeutic targets and comprehending their underlying regulatory mechanisms are crucial for treating NSCLC. Materials and methods: RNA-sequencing data from 149 lung adenocarcinoma (LUAD) patients, including 130 responders and 19 nonresponders to primary treatment, were analyzed to identify the most effective lncRNAs. The effects and regulatory pathways of the selected lncRNAs on NSCLC and cisplatin resistance were investigated. Results: Glioblastoma-downregulated RNA (GLIDR) was the most effective lncRNA in nonresponsive NSCLC patients undergoing primary treatment, and it was highly expressed in NSCLC patients and those with cisplatin-resistant NSCLC. Reducing GLIDR expression enhanced cisplatin sensitivity in resistant NSCLC and decreased the malignant characteristics of NSCLC. Moreover, bioinformatic analysis and luciferase assays revealed that microRNA-342-5p (miR-342-5p) directly targets GLIDR. MiR-342-5p overexpression inhibited NSCLC cell proliferation, migration, and invasion, whereas miR-342-5p inhibition promoted NSCLC malignancy, which was rescued by suppressing GLIDR. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PPARGC1A) was identified as a downstream target of miR-342-5p. PPARGC1A inhibition increased cisplatin sensitivity in resistant NSCLC. Moreover, PPARGC1A inhibition suppresses NSCLC malignancy, whereas PPARGC1A overexpression promoted it. Furthermore, GLIDR overexpression was found to counteract the inhibitory effects of miR-342-5p on PPARGC1A, and increased PPARGC1A expression reversed the inhibition of NSCLC malignancies caused by decreased GLIDR. Conclusions: GLIDR is a prognostic marker for cisplatin treatment in NSCLC and a therapeutic target in cisplatin-resistant NSCLC. GLIDR promotes NSCLC progression by sponging miR-342-5p to regulate PPARGC1A expression and regulates cisplatin resistance through the miR-342-5p/PPARGC1A axis, underscoring its potential as a therapeutic target in cisplatin-resistant NSCLC. [ABSTRACT FROM AUTHOR]

Background: Although a high C-reactive protein-to-albumin ratio (CAR) is believed to increase mortality risk, the association between the physical activity (PA), CAR, and mortality among cancer survivors has not been investigated. This study aimed to examine this association among cancer survivors in the United States. Methods: This cohort study used data from the National Health and Nutrition Examination Survey from 1999 to 2010. PA was self-reported using the Global Physical Activity Questionnaire, and C-reactive protein and albumin levels were obtained from laboratory data files. Mortality data were obtained by linkage of the cohort database to the National Death Index as of December 31, 2019. The analysis was conducted from November 1 to December 31, 2023. We used Cox proportional hazards multivariable regression to assess hazard ratios (HRs) and 95% confidence interval (CIs) for total and cancer-specific mortality risks attributable to PA and CAR. Results: Among 2,232 cancer survivors, 325 (14.6%) reported no PA with a high CAR. During a follow-up of up to 20.75 years (median, 12.3 years; 27,453 person-years), 1,174 deaths occurred (cancer, 335; other, 839). A high CAR was observed to be consistently associated with the highest risks of total (HR, 1.59; 95% CI, 1.37–1.85) and cancer-specific (HR, 2.06; 95% CI, 1.55–2.73) mortality compared with a low CAR in a series of adjusted models. Multivariable models showed that PA was associated with a lower risk of all-cause (HR, 0.60; 95% CI, 0.52–0.69) and cancer-specific (HR, 0.64; 95% CI, 0.49–0.84) mortality compared with no PA. In the joint analyses, survivors with PA ≥ 600 metabolic equivalent min/wk and a low CAR were more likely to reduce the risk of total (HR, 0.41; 95% CI, 0.32–0.51) and cancer-specific (HR, 0.32; 95% CI, 0.20–0.50) mortality by 59% and 68% compared with those with no PA and a high CAR. Conclusion: The pairing of adequate PA and a low CAR was significantly associated with reduced all-cause and cancer-related mortality risks. [ABSTRACT FROM AUTHOR]

Background: Protein biomarkers may contribute to the identification of vulnerable subgroups for premature mortality. This study aimed to investigate the association of plasma proteins with all-cause and cause-specific mortality among individuals with and without baseline type 2 diabetes (T2D) and evaluate their impact on the prediction of all-cause mortality in two prospective Cooperative Health Research in the Region of Augsburg (KORA) studies. Methods: The discovery cohort comprised 1545 participants (median follow-up 15.6 years; 244 with T2D: 116 total, 62 cardiovascular, 31 cancer-related and 23 other-cause deaths; 1301 without T2D: 321 total, 114 cardiovascular, 120 cancer-related and 87 other-cause deaths). The validation cohort comprised 1031 participants (median follow-up 6.9 years; 203 with T2D: 76 total, 45 cardiovascular, 19 cancer-related and 12 other-cause deaths; 828 without T2D: 169 total, 74 cardiovascular, 39 cancer-related and 56 other-cause deaths). We used Cox regression to examine associations of 233 plasma proteins with all-cause and cause-specific mortality and Lasso regression to construct prediction models for all-cause mortality stratifying by baseline T2D. C-index, category-free net reclassification index (cfNRI), and integrated discrimination improvement (IDI) were conducted to evaluate the predictive performance of built prediction models. Results: Thirty-five and 62 proteins, with 29 overlapping, were positively associated with all-cause mortality in the group with and without T2D, respectively. Out of these, in the group with T2D, 35, eight, and 26 were positively associated with cardiovascular, cancer-related, and other-cause mortality, while in the group without T2D, 55, 41, and 47 were positively associated with respective cause-specific outcomes in the pooled analysis of both cohorts. Regulation of insulin-like growth factor (IGF) transport and uptake by IGF-binding proteins emerged as a unique pathway enriched for all-cause and cardiovascular mortality in individuals with T2D. The combined model containing the selected proteins (five and 12 proteins, with four overlapping, in the group with and without T2D, respectively) and clinical risk factors improved the prediction of all-cause mortality by C-index, cfNRI, and IDI. Conclusions: This study uncovered shared and unique mortality-related proteins in persons with and without T2D and emphasized the role of proteins in improving the prediction of mortality in different T2D subgroups. [ABSTRACT FROM AUTHOR]

Background: Although nuts are a well-known healthy food group, the relationship between nut consumption and mortality remains unclear, particularly among Asians. This prospective cohort study examined the association between nut consumption and the risk of all-cause, cardiovascular disease (CVD), and cancer mortality in Korean adults. Methods: Data from two cohorts (the Ansan-Ansung and Health-Examinees) from the Korean Genome and Epidemiology Study were used. A total of 114,140 individuals aged 40–79 years were included in the data analyses. Nut consumption was assessed using a validated semi-quantitative food frequency questionnaire and categorized into four groups: non-consumers, less than 1 serving/week, 1–2 servings/week, and 2 or more servings/week (one serving was 15 g of nuts). Mortality outcomes were determined based on the 2001–2021 death records from Statistics Korea. Cox proportional hazard regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality across nut consumption categories. A stratified subgroup analysis by health-related variables was also performed. Results: During a mean follow-up of 12.3 years, 4,559 deaths were recorded. After adjusting for covariates, the HR for all-cause mortality was 0.877 (95% CI = 0.772–0.996, p for trend = 0.006) in individuals with a nut consumption of 2 or more servings/week compared with that in non-consumers. Multivariable HRs for CVD mortality were 0.800 (95% CI = 0.681–0.939) in individuals consuming less than 1 serving/week, 0.656 (95% CI = 0.469–0.918) in those consuming 1–2 servings/week, and 1.009 (95% CI = 0.756–1.347) in those consuming 2 or more servings/week compared with that in non-consumers (p for trend = 0.080). No association was observed between nut consumption and cancer mortality. Stratified analysis identified significant interactions in the association between nut consumption and all-cause mortality by age, body mass index, and physical activity. Conclusions: Nut consumption was linearly associated with the reduced risk of all-cause mortality and showed a non-linear dose-response relationship with CVD mortality in Koreans, but had no association with cancer mortality. The effects of nut consumption, which have been inadequately investigated in this population, varied across different subgroups. These findings suggest that incorporating nuts into the diet should be encouraged for long-term health of Korean adults. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) ranks among the leading causes of cancer-related mortality worldwide, posing a significant public health challenge. Despite advancements in treatment strategies, prognosis for advanced CRC remains poor. Here, we investigate the role of CLK3 and its interaction with the c-Myc signaling pathway in CRC progression. Our study reveals significant overexpression of CLK3 in CRC tumor tissues, correlating with disease advancement, and demonstrates that CLK3 promotes CRC cell proliferation, mediated by its activation of MYC signaling through upregulation of c-MYC expression. In vivo experiments confirm the oncogenic role of CLK3, with its loss resulting in decreased tumor growth and c-MYC expression. These findings highlight CLK3 as a potential therapeutic target in CRC, offering insights into novel treatment strategies. [ABSTRACT FROM AUTHOR]