Search

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]

Cervical cancer, despite being preventable through primary and secondary prevention strategies, remains one of the leading causes of morbidity and mortality among women in Brazil. This study aimed to analyze the temporal, spatial, and space-time patterns of cervical cancer mortality in Brazil. An ecological study was conducted using temporal, spatial, and space-time analysis techniques, using death certificates with cervical cancer as the underlying cause or associated condition among females in Brazil from 2000 to 2021. Death certificate and population data were provided by the Department of Health Informatics of the Unified Health System (DATASUS) and the Brazilian Institute of Geography and Statistics (IBGE), respectively. A total of 123,306 deaths associated with cervical cancer among women were registered during the study period. A rising trend in mortality was detected since 2014 onwards, after 14 years of decline. Particularly, an increase in mortality was observed among the younger age groups, and in the North and Northeast regions regardless of age. Heterogeneity in the spatial distribution of cervical cancer mortality was observed, with high mortality clusters around the country, but mostly concentrated in the North and Northeast regions. These findings suggest a need and an opportunity to develop efficient and effective health policies targeting those regions and groups of women at higher risk which in turn will allow for fast and significant reductions in cervical cancer mortality in Brazil. [ABSTRACT FROM AUTHOR]

The International Agency for Research on Cancer (IARC) classifies exposure to fine particulate matter (PM2.5) air pollution as carcinogenic to humans (Group I), most frequently associated with lung cancer. Airborne air pollutants may be associated with other sites of cancer, although few studies have examined this avenue of research. Esophageal cancer mortality rates vary substantially across townships in Taiwan, a fact that suggests environment influence. Therefore, the aim of this study was to investigate the association between long-term exposure to ambient PM2.5 and deaths attributed to esophageal cancer in 66 municipal areas across Taiwan. To conduct this study, annual PM2.5 levels were determined taking into account age-standardized esophageal cancer mortality rates in male and female residents of these municipalities from 2012 to 2021. The annual PM2.5 levels of each municipality were divided into tertiles and computed adjusted risk ratio (RR) using weighted-multiple regression analyses controlling for municipal lung cancer deaths, urbanization level, and physician density. Men residing in those areas with intermediate PM2.5 tertile levels (18.96–25.19 ug/m3) were found to have an adjusted RR of 1.22 (1.15–1.30) and those of residing areas with the highest tertiles levels (25.20–29.48 ug/m3) exhibited an RR of 1.11 (1.051.18). However, in women in the same municipalities, a significant inverse association was found between PM2.5 levels and mortality attributed to esophageal cancer, 0.82 (95% CI = 0.65-1.04) and 0.61 (95% CI = 0.47-0.79), respectively. These findings suggest that long-term exposure to PM2.5 increases the risk of developing esophageal cancer in men in Taiwan. [ABSTRACT FROM AUTHOR]

Lung cancer accounts for the highest cancer-related mortality worldwide. While immunotherapies targeting anti-tumor immune responses have demonstrated efficacy in clinical practice, the demand for novel treatment modalities remains urgent. Oncolytic viruses (OVs), which selectively kill tumor cells while stimulating an anti-tumor immune response, represent a potential breakthrough in lung cancer therapy. The induction of anti-tumor immunity by OVs is central to their overall therapeutic effectiveness. Many natural receptors on the surface of cancer cells are dysregulated, providing potential entry points for OVs. Furthermore, the inherent dysregulation of some key signaling pathways in lung cancer cells promotes proliferation, progression and metastasis, which may facilitate selective viral replication. In this review, we explore the application of OVs in lung cancer by analyzing several major OVs and their corresponding entry receptors. Then, we also examine the key signaling pathways and molecules with the potential to synergize with OVs in modulating the immune tumor microenvironment. Finally, we discuss the combination and administration strategies that warrant further clinical trials for validation. Despite certain limitations, the tolerability of OVs positions virotherapy as a promising avenue in the future of lung cancer treatment. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Design Measurements Results Conclusions This study examined the indirect effects of the number of Japanese municipal public health nurses (PHNs) on cancer standardized mortality ratios (SMRs), using cancer screening and diagnostic follow‐up rates as mediators.Ecological study using municipalities as the unit of analysisAggregate, municipal‐level government data were analyzed using a linear model with empirical Bayes estimates of SMRs (EBSMRs) for gastric, colorectal, and lung cancers as the dependent variables, and the number of PHNs, cancer screening rate, diagnostic follow‐up rate, and adjustment variables as independent variables. Structural equation modeling (SEM) was used to examine the indirect effects of PHNs.Cancer screening rates were significantly negatively associated with EBSMR, except for gastric cancer in women. No significant association was observed between the EBSMR and diagnostic follow‐up rates. SEM revealed a significant indirect effect of the number of PHNs, most of which was due to the cancer screening rate.From a population‐based public health perspective, increasing the number of PHNs and focusing on improving cancer screening rates may effectively reduce cancer SMRs. [ABSTRACT FROM AUTHOR]

AbstractBreast cancer (BC) is a major cause of cancer-related mortality across the globe and is especially highly prevalent in females. Based on the poor outcomes and several limitations of present management approaches in BC, there is an urgent need to focus and explore an alternate target and possible drug candidates against the target in the management of BC. The accumulation of misfolded proteins and subsequent activation of unfolded protein response (UPR) alters the homeostasis of endoplasmic reticulum (ER) lumen that ultimately causes oxidative stress in ER. The UPR activates stress-detecting proteins such as IRE1α, PERK, and ATF6, these proteins sometimes may lead to the activation of pro-apoptotic signaling pathways in cancerous cells. The ER stress-dependent antitumor activity could be achieved either through suppressing the adaptive UPR to make cells susceptible to ER stress or by causing chronic ER stress that may lead to triggering of pro-apoptotic signaling pathways. Several herbal drugs trigger ER-dependent apoptosis in BC cells. Therefore, this review discussed the role of fifty-two herbal drugs and their active constituents, focusing on disrupting the balance of the ER within cancer cells. Further, several challenges and opportunities have also been discussed in ER-dependent management in BC.Breast cancer (BC) is a major cause of cancer-related mortality across the globe and is especially highly prevalent in females. Based on the poor outcomes and several limitations of present management approaches in BC, there is an urgent need to focus and explore an alternate target and possible drug candidates against the target in the management of BC. The accumulation of misfolded proteins and subsequent activation of unfolded protein response (UPR) alters the homeostasis of endoplasmic reticulum (ER) lumen that ultimately causes oxidative stress in ER. The UPR activates stress-detecting proteins such as IRE1α, PERK, and ATF6, these proteins sometimes may lead to the activation of pro-apoptotic signaling pathways in cancerous cells. The ER stress-dependent antitumor activity could be achieved either through suppressing the adaptive UPR to make cells susceptible to ER stress or by causing chronic ER stress that may lead to triggering of pro-apoptotic signaling pathways. Several herbal drugs trigger ER-dependent apoptosis in BC cells. Therefore, this review discussed the role of fifty-two herbal drugs and their active constituents, focusing on disrupting the balance of the ER within cancer cells. Further, several challenges and opportunities have also been discussed in ER-dependent management in BC. [ABSTRACT FROM AUTHOR]

Summary: Background: Elevated allostatic load (AL) has been associated with the risk and poor prognosis of many chronic diseases. The association between AL and inflammatory bowel disease (IBD) is unknown. Aims: The aim of this study is to investigate the associations between AL and the risk and prognosis of IBD. Methods: We included 326,345 adults and 3767 patients with IBD from the UK Biobank. AL served as the exposure, estimated using the AL biomarker panel, with the primary outcomes including the risk and prognosis of IBD. We used Cox regression models to examine the associations. Results: High AL biomarker panel was associated with a greater risk of IBD (hazard ratio: 1.19, 95% CI: 1.08–1.31), ulcerative colitis (1.17, 95%CI: 1.04–1.32), and Crohn's disease (1.25, 95%CI: 1.05–1.49). Risk of developing IBD increased by 12% in quartile 2, 20% in quartile 3, and 37% in quartile 4 as AL biomarker panel increased. The all‐cause mortality risk in IBD compared with quartile 1 rose by 54% for quartile 2, 72% for quartile 3, and 82% for quartile 4, as AL biomarker panel increased. Similar effects were also observed for ulcerative colitis and Crohn's disease. An increase in AL biomarker panel count was associated with an elevated risk of intestinal resection and colorectal cancer in IBD. Conclusions: Increased AL is associated with IBD risk, as well as the risks of intestinal resection, colorectal cancer and mortality. [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 nationwide HUN-CANCER EPI study examined cancer incidence and mortality rates in Hungary from 2011 to 2019. Methods: Using data from the National Health Insurance Fund (NHIF) and Hungarian Central Statistical Office (HCSO), our retrospective study analyzed newly diagnosed malignancies between Jan 1, 2011, and Dec 31, 2019. Agestandardized incidence and mortality rates were calculated for all and for different tumor types using both the 1976 and 2013 European Standard Populations (ESP). Findings: The number of newly diagnosed cancer cases decreased from 60,554 to 56,675 between 2011-2019. Age-standardized incidence rates were much lower in 2018, than previously estimated (475.5 vs. 580.5/100,000 person-years [PYs] in males and 383.6 vs. 438.5/100,000 PYs in females; ESP 1976). All-site cancer incidence showed a mean annual decrease of 1.9% (95% CI: 2.4%-1.4%) in men and 1.0% (95% CI:1.42%-0.66%) in women, parallel to mortality trends (-1.6% in males and -0.6% in females; ESP 2013). In 2018, the highest age-standardized incidence rates were found for lung (88.3), colorectal (82.2), and prostate cancer (62.3) in men, and breast (104.6), lung (47.7), and colorectal cancer (45.8) in women. The most significant decreases in incidence rates were observed for stomach (4.7%), laryngeal (4.4%), and gallbladder cancers (3.5%), with parallel decreases in mortality rates (3.9%, 2.7% and 3.2%, respectively). Interpretation: We found a lower incidence of newly diagnosed cancer cases for Hungary compared to previous estimates, and decreasing trends in cancer incidence and mortality, in line with global findings and the declining prevalence of smoking. [ABSTRACT FROM AUTHOR]

Introduction: Multiple myeloma (MM) is a leading cause of hematopoietic cancer-related mortality, accounting for 20% of deaths. MM-targeted therapies have demonstrated efficacy, and since 2015, the United States Food and Drug Administration (FDA) has approved five targeted drugs. However, their cardiovascular safety has not been comprehensively evaluated. Objective: This study aimed to investigate the association between MM-targeted therapy and cardiovascular adverse events (AEs). Methods: Disproportionality analysis was conducted on reports from the FDA AE Reporting System database from 2014 to the second quarter of 2023. Cardiovascular AEs were grouped into nine narrow categories using the Standardized Medical Dictionary for Regulatory Activities Queries (SMQs). Results: A total of 3,228 cardiovascular AE cases involving MM-targeted therapy were extracted and analyzed. Significant disproportionality was identified for daratumumab, elotuzumab, and isatuximab. Among the nine narrow SMQ categories, the three most reported cardiovascular AEs were cardiomyopathy, cardiac arrhythmias, and embolic and thrombotic events. Noninfectious myocarditis/pericarditis, cardiac arrhythmias, and embolic and thrombotic events exhibited the strongest signal strengths. The cardiovascular AE risk was higher within the first month and gradually decreased thereafter; however, it increased rapidly again after 1 year. This trend was observed for all cardiovascular AEs. The Kaplan-Meier curve and the log-rank test revealed that isatuximab and elotuzumab exhibited a significantly lower probability of cardiovascular AEs than daratumumab (p < 0.001). Conclusions: MM-targeted therapy is significantly associated with an increased risk of previously unknown cardiovascular AE profiles, with the range and onset differing among various drugs, thereby warranting specific monitoring and appropriate management. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC), a common type of malignant tumor, ranks as the sixth highest contributor to cancer-related mortality worldwide. Due to the condition that most patients with EC are diagnosed at advanced or metastatic status, the efficacy of conventional treatments including surgery, chemotherapy and radiotherapy is limited, resulting in a dismal 5-year overall survival rate. In recent years, the application of immune checkpoint inhibitors (ICIs) has presented a novel therapeutic avenue for EC patients. Both ICIs monotherapy and immunotherapy combined with chemotherapy or chemoradiotherapy (CRT) have demonstrated marked benefits for patients with advanced EC. Adjuvant or neoadjuvant therapy incorporating immunotherapy has also demonstrated promising prospects in the context of perioperative treatment. Nonetheless, due to the variable response observed among patients undergoing immunotherapy, it is of vital importance to identify predictive biomarkers for patient stratification, to facilitate identification of subgroups who may derive greater benefits from immunotherapy. In this review, we summarize validated or potential biomarkers for immunotherapy in EC in three dimensions: tumor-cellassociated biomarkers, tumor-immune microenvironment (TIME)-associated factors, and host-associated biomarkers, so as to provide a theoretical foundation to inform tailored therapy for individuals diagnosed with EC. [ABSTRACT FROM AUTHOR]

COVID‐19 pandemic has had a substantial effect on healthcare systems worldwide, including the care of patients with lung cancer. The impact of healthcare disruptions and behavioral changes on lung cancer mortality is unclear. Patients newly diagnosed with lung cancer during the pandemic period 2020–2021 were compared with those diagnosed in the pre‐pandemic 2018–2019. The primary outcome was all‐cause mortality within 1 year. Cox proportional hazards regression analyses were conducted to estimate the changes in mortality between pandemic and pre‐pandemic. Multiple mediation analyses were performed to determine the factors that accounted for the changes in mortality. In total, 5785 patients with lung cancer were included in this study. The overall mortality rate was significantly higher during the pandemic compared with the pre‐pandemic (crude hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.05, 1.29). Mediation analyses showed that not receiving tumor‐directed treatment, diagnosis at an older age, and decreased diagnosis through cancer screening significantly accounted for 17.5% (95%CI: 4.2, 30.7), 13.9% (95%CI: 0.8, 27.0), and 12.4% (95%CI: 3.0, 21.8) of the increased mortality, respectively. This study revealed a significant increase in mortality risk in patients with lung cancer who have not received tumor‐directed treatment or cancer screening, despite potential selection bias for follow‐up status. Efforts should be focused on ensuring timely access to healthcare services, optimizing treatment delivery, and addressing the unique challenges faced by patients with lung cancer during the pandemic to mitigate the impact of the pandemic on lung cancer outcomes and provide clinical care to vulnerable populations. [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: 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: 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]

Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. Despite the widespread recognition of tumor immunotherapy in treating unresectable GC, challenges, including ineffective immunotherapy and drug resistance, persist. Therefore, understanding the regulatory mechanisms of PD-L1, particularly in the context of super-enhancers (SEs) and zinc finger protein 36 ring finger protein-like 1 (ZFP36L1) RNA-binding protein, is crucial. In this study, we performed H3K27ac Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing, investigated the heterogeneity of SEs between two GC subtypes with differential growth patterns, and revealed the immune escape signatures driven by ZFP36L1-SE in infiltrative GC through SEs inhibitors treatment. The regulation of ZFP36L1 to PD-L1 was evaluated by quantitative PCR, western blot, flow cytometry, and immunohistochemistry. Furthermore, we explored its regulatory mechanisms using a combination of molecular biology techniques, including luciferase reporter assay, GST/RNA pull-down, chromatin immunoprecipitation (ChIP)/RIP experiments, and in vivo functional assays. We demonstrated that ZFP36L1, driven by an SE, enhances IFN-γ-induced PD-L1 expression, with SPI1 identified as the specific transcription factor binding to ZFP36L1-SE. Mechanistically, ZFP36L1 binds to the adenylate uridylate-rich element in the 3' untranslated region (3'UTR) of HDAC3 mRNA, exacerbating its mRNA decay, and thereby facilitating PD-L1 abnormal transcriptional activation. Collectively, our findings provide mechanistic insights into the role of the SPI1-ZFP36L1-HDAC3-PD-L1 signaling axis in orchestrating immune escape mechanisms in GC, thereby offering valuable insights into the potential targets for immune checkpoint therapy in GC management. [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: Prostate cancer (PCa) is a leading cause of cancer-related mortality among men, characterized by significant heterogeneity that complicates diagnosis and treatment. Methods and results: To enhance our understanding of PCa, we utilized single-cell RNA sequencing (scRNA-seq) data to identify distinct malignant epithelial cell subpopulations and their molecular characteristics. By integrating scRNA-seq data with bulk RNA-seq data, we constructed a prognostic risk score model. The influence of key genes identified in the risk score on PCa was validated through both in vitro and in vivo experiments. Our study revealed eight unique malignant epithelial cell clusters, each exhibiting distinct molecular characteristics and biological functions. KEGG and GO enrichment analyses highlighted their involvement in various pathways. The prognostic risk score model demonstrated strong predictive power for patient outcomes, particularly in predicting progression-free survival (PFS). Notably, KLHL17, identified as a high-risk gene, was found to significantly impact PCa cell proliferation, migration, invasion, and apoptosis upon knockdown. This finding was further validated in vivo using a subcutaneous xenograft tumor model, where reduced KLHL17 expression led to decreased tumor growth. Conclusion: Our research provides a comprehensive analysis of PCa heterogeneity and highlights KLHL17 as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Globally, cervical cancer remains the leading cause of cancer death in women in many countries and in the United States it is the second most common cause of cancer death in younger women age 20--39 years. Distance from treatment facility may contribute to treatment delay and ultimately, disease outcomes. We hypothesize that greater distance from the treating facility results in a treatment delay among women with non-metastatic cervical cancer. Data for 36,986 subjects with non-metastatic cervical cancer treated with definitive radiation or surgery between 2004 and 2015 were selected from the National Cancer Database. Subjects were excluded if they had missing information, variant histology, treatment >180 days from diagnosis, or lived >1000 miles from their facility. Univariate comparisons were performed using chi-square and analysis of variance. Multivariable linear regression was used to investigate the effect of distance quartile on time to treatment while adjusting for significant patient and disease characteristics. Results: The mean age was 49.5 years, 16.2% of women were black, 14.2% were Hispanic, 48.7% had private insurance, 98.4% lived in urban/metro counties, and 56.1% received surgery versus radiation as initial treatment. Multivariable analysis identified a treatment delay of 1.1 days for distance quartile 2 (p = 0.008), 2.0 days for quartile 3 (p< 0.001), and 4.0 days for quartile 4 (p<0.001) compared to women in the closest quartile. Other patient and disease characteristics were significantly associated with treatment delay. Interestingly, women living in rural counties were treated over 8.5 days earlier than those from the most populous metropolitan counties (p < 0.001). In conclusion: Greater distance from treatment facility resulted in a statistically significant delay in treatment. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a leading cause of cancer-related mortality in women, with a rising incidence globally. Neoadjuvant chemotherapy(NACT) is a standard treatment approach for operable advanced loco-regional breast cancer, aiming to achieve tumor shrinkage, downstaging, and improved surgical outcomes. GATA3 expression has been identified as a significant marker for tumor differentiation, estrogen receptor status, and clinical outcomes in breast cancer. Objectives: To investigate the expression of GATA3 in post-NACT breast carcinoma cases and its utility in confirming histopathological diagnosis of partial and complete response, thereby guiding treatment strategies and predicting patient outcomes. Methods: A cross-sectional study of 60 breast carcinoma cases treated with NACT was conducted at Mysore Medical College and Research Institute. GATA3 expression was evaluated using immunohistochemistry, and its correlation with histopathological response to chemotherapy was assessed. Results: Among 60 cases, GATA3 was expressed in 87% of cases, with 91% of partial responders and 73% of complete responders showing immunopositivity. The study demonstrates GATA3 expression in post-NACT breast carcinoma cases, highlighting its potential as a predictive marker for treatment outcomes. Conclusion: GATA3 is a valuable marker for predicting response to NACT in breast cancer patients, supporting its utility in confirming histopathological diagnosis, guiding treatment strategies, and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is the third most common cancer and the second highest cause of cancer mortality in Australia. Despite advances in colorectal surgery, anastomotic leak still occurs in low‐risk patients and is a substantial cause of morbidity and mortality. Many operative strategies are used to assess anastomotic integrity such as an air leak test or intraoperative flexible sigmoidoscopy, however an objective anastomotic checklist is yet to be developed and studied. This study aims to develop a photodocumentary anastomotic specific checklist and determine its feasibility for implementation. Methods: Patients undergoing left sided colorectal resections with primary anastomosis without a de‐functioning ileostomy were prospectively included between May 2021 and December 2022. A photographic checklist assessing anastomotic perfusion, integrity via either air test or endoscopic image, evidence of complete operative doughnut specimens and the assessment of tension was implemented. The feasibility of an anastomotic checklist was externally validated by four independent colorectal surgeons from Australia, New Zealand and United States of America. Results: The anastomotic checklist was completed in 44 patients. Mean age was 62 years, with 43% male and mean BMI 28. Operations included high anterior resection (45%), low anterior resection (18%), ultra‐low anterior resection (20%), reversal of Hartmann's (11%). Median length of stay was 4 days. Complications post operatively were documented in six patients with anastomotic leak in 2% and wound infection in 6.8%. Intraclass correlation coefficients were poor amongst all reviewers with air leak and tension having no inter‐reviewer correlation. Conclusion: The introduction of an anastomotic checklist was a feasible tool to systematically assess and document anastomotic integrity. Unfortunately, with the small sample size there was significant discrepancy in inter‐observer variability, and this led to poor correlation regarding which patients were typically high risk requiring a temporary ileostomy. Larger studies on the implementation of an anastomotic checklist will be needed to evaluate if it is an inherently feasible approach and if there is an effect on anastomotic leak. [ABSTRACT FROM AUTHOR]

Background: Estimating prognosis can be a barrier to timely palliative care involvement. The modified Hospitalized‐patient One‐year Mortality Risk (mHOMR) score uses hospital admission data to calculate the risk of death within 12 months and may be a useful tool to trigger a referral to palliative care. Methods: The mHOMR tool was retrospectively applied to consecutive acute admissions to a quaternary cancer center in Toronto, Canada from March 1 to May 31, 2018. The study aimed to investigate the association between dichotomized mHOMR scores (the cohort median score of 0.27 and the developer‐recommended score of 0.21) and the risk of death, and whether these could be used to identify patients who may benefit from timely palliative care involvement. Results: Of 269 inpatients, 87 were elective admissions and excluded from further analyses. At the median mHOMR score of 0.27, 91/182 patients (50%) were categorized as high‐risk of death within 12 months (mHOMR+), 53 (58%) were referred to palliative care. At the lower cut‐off of 0.21, 103 patients were mHOMR+, of whom 57 (55.3%) were referred to palliative care. The higher mHOMR was significantly associated with mortality (29.7% mHOMR− vs. 39.8% mHOMR+ at 12 months, log‐rank p < 0.05). The association between the developer‐recommended mHOMR cut‐off (≥ 0.21) and mortality was not significant (p = 0.15). Conclusions: A higher mHOMR score was significantly associated with the risk of mortality in patients with advanced cancer. However, the developer‐recommended mHOMR cut‐off of 0.21 failed to identify a statistically significant difference between patients with advanced cancer at low versus high scores. While mHOMR may be a useful tool to augment clinical judgment and identify inpatients with advanced cancer at high risk of death, who in turn may benefit from referral to palliative care, the optimal mHOMR cutoff may warrant adjustment for this population. [ABSTRACT FROM AUTHOR]

Background: The associations between hysterectomy and cardiovascular disease (CVD) and mortality remains unlcear and a meta‐analysis with cohort studies is lacking. Objectives: This study aimed to conduct a systematic review and meta‐analysis of cohort studies to investigate the relationship between hysterectomy and CVD, coronary heart disease (CHD), stroke, heart failure, and all‐cause, cardiovascular and cancer mortality. We further explored the effect of oophorectomy on the association between hysterectomy and these health outcomes. Search strategy: PubMed, EMBASE and Web of Science were searched up to 24 July 2023. Selection criteria: Cohort studies. Data collection and analysis: Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were pooled using a random‐effects model. We used I2 to assess the heterogeneity between studies. Main results: Forty‐three studies were included in the meta‐analysis. Hysterectomy was significantly associated with an increased risk of CVD (pooled HR 1.11, 95% CI 1.09–1.13; n = 6; I2 = 0) and stroke (HR 1.09, 95% CI 1.04–1.14; n = 7; I2 = 52%), but with a decreased risk of cancer mortality (HR 0.93, 95% CI 0.86–1.00; n = 4; I2 = 81%). No significant association was observed between hysterectomy and CHD (n = 10; I2 = 83%), all‐cause mortality (n = 8; I2 = 81%) or cardiovascular mortality (n = 7; I2 = 89%). Hysterectomy with and without oophorectomy was significantly associated with CVD and stroke risk, but showed a larger effect size for hysterectomy with oophorectomy. A significantly increased risk of CHD was observed in the subgroup of hysterectomy with oophorectomy, but not for the subgroup of hysterectomy alone. Conclusions: Hysterectomy may increase the risk of CVD, CHD and stroke, but not all‐cause, cardiovascular or cancer mortality. Hysterectomy with oophorectomy may have a higher risk of CVD, CHD and stroke than hysterectomy alone. However, the results on CHD and mortality related to hysterectomy should be interpreted cautiously because of the high level of heterogeneity and unstable subgroup analyses. [ABSTRACT FROM AUTHOR]

High circulating vitamin D levels and supplementation may lower prostate cancer mortality. To probe for direct effects of vitamin D signaling in the primary tumor, we assessed how activation of intratumoral vitamin D signaling in prostate cancer is associated with lethal prostate cancer during long-term follow-up. Among 404 participants with primary prostate cancer in the Health Professionals Follow-up Study and the Physicians' Health Study, we defined a gene score of expected activated intratumoral vitamin D signaling consisting of transcriptionally upregulated (CYP27A1 , CYP2R1 , RXRA , RXRB , and VDR) and downregulated genes (CYP24A1 and DHCR7). We contrasted vitamin D signaling in tumors that progressed to lethal disease (metastases/prostate cancer-specific death, n  = 119) over up to three decades of follow-up with indolent tumors that remained nonmetastatic for >8 years post-diagnosis (n  = 285). The gene score was downregulated in tumor tissue compared with tumor-adjacent histologically normal tissue of the same men. Higher vitamin D gene scores were inversely associated with lethal prostate cancer (odds ratio for highest versus lowest quartile: 0.46, 95% confidence interval: 0.21–0.99) in a dose–response fashion and after adjusting for clinical and pathologic factors. This association appeared strongest among men with high predicted plasma 25-hydroxyvitamin D3 and men with body mass index ≥25 kg/m2. Findings were replicated with broader gene sets. These data support the hypothesis that active intratumoral vitamin D signaling is associated with better prostate cancer outcomes and provide further rationale for testing how vitamin D-related interventions after diagnosis could improve prostate cancer survival through effects on the tumor. [ABSTRACT FROM AUTHOR]

Metastasis is the leading cause of cancer-related mortality; however, a complete understanding of the molecular programs driving the metastatic cascade is lacking. Metastasis is dependent on collective invasion—a developmental process exploited by many epithelial cancers to establish secondary tumours and promote widespread disease. The key drivers of collective invasion are "Leader Cells", a functionally distinct subpopulation of cells that direct migration, cellular contractility, and lead trailing or follower cells. While a significant body of research has focused on leader cell biology in the traditional context of collective invasion, the influence of metastasis-promoting leader cells is an emerging area of study. This review provides insights into the expanded role of leader cells, detailing emerging evidence on the hybrid epithelial–mesenchymal transition (EMT) state and the phenotypical plasticity exhibited by leader cells. Additionally, we explore the role of leader cells in chemotherapeutic resistance and immune evasion, highlighting their potential as effective and diverse targets for novel cancer therapies. [ABSTRACT FROM AUTHOR]

Background Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the "intended effect" (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests. Methods We simulated hypothetical MCD screening trials to compare power and sample size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial [NLST], Minnesota Colon Cancer Control Study [MINN-FOBT-A], and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial—colorectal component [PLCO-CRC]). Results Compared with the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality P values 6-fold (NLST), 33-fold (MINN-FOBT-A), or 260 000-fold (PLCO-CRC) or, alternately, reduced sample size (90% power) by 25% (NLST), 47% (MINN-FOBT-A), or 63% (PLCO-CRC). For potential MCD trial designs requiring 100 000 subjects per arm to achieve 90% power for multicancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37 500-50 000 per arm, depending on assumptions concerning control-arm test-positives. Conclusions Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample size or accelerate trials and could provide particularly strong power gains for MCD tests. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Adequate bowel preparation is paramount for a high-quality screening colonoscopy. Despite the importance of adequate bowel preparation, there is a lack of large studies that associated the degree of bowel preparation with long-term colorectal cancer outcomes in screening patients. METHODS: In a large population-based screening program database in Austria, quality of bowel preparation was estimated according to the Aronchick Scale by the endoscopist (excellent, good, fair, poor, and inadequate bowel preparation). We used logistic regression to assess the influence of bowel preparation on the detection of different polyp types and the interphysician variation in bowel preparation scoring. Time-to-event analyses were performed to investigate the association of bowel preparation with postcolonoscopy colorectal cancer (PCCRC) death. RESULTS: A total of 335,466 colonoscopies between January 2012 and follow-up until December 2022 were eligible for the analyses. As compared with excellent bowel preparation, adenoma detection was not significantly lower for good bowel preparation (odds ratio 1.01, 95% confidence interval [CI] 0.9971-1.0329, P 5 0.1023); however, adenoma detection was significantly lower in fair bowel preparation (odds ratio 0.97, 95% CI 0.9408-0.9939, P 5 0.0166). Individuals who had fair or lower bowel preparation at screening colonoscopy had significantly higher hazards for PCCRC death (hazard ratio for fair bowel preparation 2.56, 95% CI 1.67-3.94, P < 0.001). DISCUSSION: Fair bowel preparation on the Aronchick Scale was not only associated with a lower adenoma detection probability but also with increased risk of PCCRC death. Efforts should be made to increase bowel cleansing above fair scores. [ABSTRACT FROM AUTHOR]

Background The healthy worker effect may distort the association between exposure and health effects in workers. However, few studies have investigated both the healthy worker hire and survival effects simultaneously, and they are limited to mortality studies in male workers. Methods We utilized a data set comprising South Korean diagnostic medical radiation workers registered in the National Dose Registry between 1996 and 2011, and merged it with mortality and cancer incidence data. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were computed for comparison with the general population. To account for time-varying confounders influenced by prior occupational radiation exposure, we applied g-estimation using structural nested accelerated failure time models and compared the outcomes with those from Weibull regression. Results A total of 1831 deaths and 3759 first primary cancer cases were identified among 93 918 workers. Both male (SMR = 0.44; 95% CI: 0.42, 0.46) and female workers (SMR = 0.53; 95% CI: 0.46, 0.60) showed lower mortality rates compared with national rates. In the SIR analysis, male workers exhibited reduced risks of solid cancer whereas female workers had increased risks. The g-estimation-derived hazard ratios (HRs) from radiation exposure exceeded those from Weibull regression estimates for all-cause death (HR = 2.55; 95% CI: 1.97, 3.23) and all-cancer incidence (HR = 1.96; 95% CI: 1.52, 2.55) in male workers whereas female workers showed the opposite results. Conclusions Comprehensive consideration of the healthy worker effect by sex is essential for estimating the unbiased impact of occupational exposure on health outcomes, notably in studies focusing on male mortality. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Our study aimed to evaluate the association between the metabolic score for visceral fat (METS‐VF) and mortality.We conducted a cohort study comprising 11,120 participants. We employed weighted multivariable Cox regression analysis to assess the relationship between METS‐VF and mortality. Restricted cubic spline analyses were used to investigate potential non‐linear associations. Receiver operating characteristic curves were used to evaluate the predictive value of METS‐VF and other obesity‐related indicators for mortality. Subgroup analysis and sensitivity analysis were performed to confirm the robustness of the results. Mendelian randomization analysis was utilized to assess potential causality.Over a median follow‐up duration of 83 months, a total of 1014 all‐cause deaths, 301 cardiovascular deaths, and 262 cancer deaths occurred. For every 0.2‐unit increase in METS‐VF, the hazard ratios(HRs) of all‐cause mortality, cardiovascular mortality, and cancer mortality were 1.13 [95% confidence interval (CI): 1.06, 1.20], 1.18 (95% CI: 1.06, 1.31), and 1.13 (95% CI: 1.03, 1.25), respectively. In addition, restricted cubic spline analyses revealed no significant non‐linear associations between METS‐VF and all‐cause mortality, cardiovascular mortality, and cancer mortality. In multivariate Cox regression models, hazard ratios of all‐cause mortality, cardiovascular mortality and cancer mortality were higher in the highest METS‐VF group compared to the reference group. Subgroup and sensitivity analyses confirmed that our results were robust. Receiver operating characteristic curves indicated that METS‐VF predicted mortality better than other obesity‐related indicators. Mendelian randomization analysis confirmed significant causal relationships.METS‐VF was positively associated with all‐cause mortality, cardiovascular mortality, and cancer mortality. These findings suggest that METS‐VF could serve as a straightforward, reliable, and cost‐effective marker for identifying individuals at high risk of mortality. [ABSTRACT FROM AUTHOR]

Introduction: Hepatocellular carcinoma (HCC) constitutes the majority of liver cancers and significantly impacts global cancer mortality. While ultrasound (US) with or without alpha‐fetoprotein is the mainstay for HCC surveillance, its limitations highlight the necessity for more effective surveillance tools. Therefore, this review explores evolving imaging modalities and abbreviated magnetic resonance imaging (MRI) (AMRI) protocols as promising alternatives, addressing challenges in HCC surveillance. Areas Covered: This comprehensive review delves into the evaluation and challenges of HCC surveillance tools, focusing on non‐contrast abbreviated MRI (NC‐AMRI) and contrast‐enhanced abbreviated MRI protocols. It covers the implementation of AMRI for HCC surveillance, patient preferences, adherence, and strategies for optimizing cost‐effectiveness. Additionally, the article provides insights into prospects for HCC surveillance by summarizing meta‐analyses, prospective studies, and ongoing clinical trials evaluating AMRI protocols. Expert Opinion: The opinions underscore the transformative impact of AMRI on HCC surveillance, especially in overcoming US limitations. Promising results from NC‐AMRI protocols indicate its potential for high‐risk patient surveillance, though prospective studies in true surveillance settings are essential for validation. Future research should prioritize risk‐stratified AMRI protocols and address cost‐effectiveness for broader clinical implementation, alongside comparative analyses with US for optimal surveillance strategies. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review and meta-analysis aimed to examine the impact of global quality of life (QOL) on mortality risk in patients with cancer, considering cancer type and timepoint of QOL assessment. Methods: A systematic search was conducted using Cumulated Index to Nursing and Allied Health Literature, PubMed/MEDLINE, and Scopus databases from inception to December 2022. Observational studies that assessed QOL and examined mortality risk in patients with cancer were extracted. Subgroup analyses were performed for cancer types and timepoints of QOL assessment. Results: Overall, global QOL was significantly associated with mortality risk (hazard ratio: 1.06, 95% confidence interval: 1.05–1.07; p < 0.00001). A subgroup analysis based on cancer type demonstrated that lung, head and neck, breast, esophagus, colon, prostate, hematologic, liver, gynecologic, stomach, brain, bladder, bone and soft tissue, and mixed type cancers were significantly associated with mortality risk; however, melanoma and pancreatic cancer were not significantly associated with mortality risk. Additionally, global QOL was associated with mortality risk at all timepoints (pretreatment, posttreatment, and palliative phase); pretreatment QOL had the largest impact, followed by posttreatment QOL. Conclusion: These findings provide evidence that QOL is associated with mortality risk in patients with cancer at any timepoint. These results indicate the importance of evaluating the QOL and supportive interventions to improve QOL in any phase. [ABSTRACT FROM AUTHOR]

Despite being the leading cause of cancer-related childhood mortality, pediatric gliomas have been relatively understudied, and the repurposing of immunotherapies has not been successful. Whole-transcriptome sequencing, single-cell sequencing, and sequential multiplex immunofluorescence were used to identify an immunotherapeutic strategy that could be applied to multiple preclinical glioma models. MAPK-driven pediatric gliomas have a higher IFN signature relative to other molecular subgroups. Single-cell sequencing identified an activated and cytotoxic microglia (MG) population designated MG-Act in BRAF-fused, MAPK-activated pilocytic astrocytoma (PA), but not in high-grade gliomas or normal brain. T cell immunoglobulin and mucin domain 3 (TIM3) was expressed on MG-Act and on the myeloid cells lining the tumor vasculature but not normal brain vasculature. TIM3 expression became upregulated on immune cells in the PA microenvironment, and anti-TIM3 reprogrammed ex vivo immune cells from human PAs to a proinflammatory cytotoxic phenotype. In a genetically engineered murine model of MAPK-driven, low-grade gliomas, anti-TIM3 treatment increased median survival over IgG- and anti–PD-1–treated mice. Single-cell RNA-Seq data during the therapeutic window of anti-TIM3 revealed enrichment of the MG- Act population. The therapeutic activity of anti-TIM3 was abrogated in mice on the CX3CR1 MG–KO background. These data support the use of anti-TIM3 in clinical trials of pediatric low-grade, MAPK-driven gliomas. [ABSTRACT FROM AUTHOR]

Background Aluminium industry workers are at risk of long-term health consequences. Aims To investigate mortality and cancer incidence in bauxite mine and alumina refinery workers. Methods A pre-existing cohort of workers was re-linked with the Australian National Death Index, and the Australian Cancer Database to provide additional death (7 years) and cancer (9 years) data. Standardized mortality ratios (SMRs) and standardized incidence rates (SIRs) were estimated by job category, duration of employment and time since first employment. Results Linkage was performed for 6935 (6207 male) workers. Compared with the general population, there was a reduced or similar risk of death for mine/refinery workers for all causes except mesothelioma which was increased amongst male production workers [SMR 2.42, 95% CI 1.11–4.60]. Mesothelioma incidence was also increased amongst males [SIR 2.50, 95% CI 1.60–3.71]. Male office workers had a greater incidence of prostate cancer [SIR 1.30, 95% CI 1.06–1.57] and thyroid cancer [SIR 3.47, 95% CI 1.66–6.38]. Melanoma incidence was increased in female office workers [SIR 2.27, 95% CI 1.36–3.54]. Lip cancer incidence was increased in male maintenance/production workers [SIR 2.04, 95% CI 1.02–3.65]. Overall cancer incidence was otherwise similar to the general Australian population. Conclusions Overall risk of death and incidence of cancer for bauxite mine and alumina refinery workers was similar to the general population. Incidence and risk of death from mesothelioma were higher, likely due to historic asbestos exposure in this and other industries. The increased risk of melanoma, lip, prostate and thyroid cancers requires further investigation. [ABSTRACT FROM AUTHOR]

Public health measures necessitated by the COVID-19 pandemic have affected cancer pathways by halting screening, delaying diagnostic tests and reducing the numbers starting treatment. Specifically, this moves individuals from observed and treated pathways to unobserved and untreated pathways. We introduce a semi-Markov model that includes both, extending an industry-based multiple state model used for life and critical illness insurance. Our model includes events related to cancer diagnosis and progression based on publicly available population data for women aged 65–89 in England and on relevant medical literature. We quantify age-specific excess deaths, for a period up to 5 years, along with years of life expectancy lost and changes in cancer mortality by cancer stage. Our analysis suggests a 3–6% increase in breast cancer deaths, and a 4–6% increase in registrations of advanced breast cancer, robust under sensitivity analysis. This should be applicable to actuarial work in areas where longevity and advanced age morbidity affect healthcare, retirement and insurance. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion We have previously shown that exposure to famine in early gestation was associated with poorer adult health and, in women, with reduced survival up to age 64.Here, we explore the association between prenatal famine exposure and mortality up to age 76 for men and women separately.We studied adult mortality (>18 years) in men (n = 989) and women (n = 1002) born as term singletons around the time of the 1944–1945 Dutch famine. We compared overall and cause‐specific mortality among men and women exposed to famine in late, mid, or early gestation to that among unexposed persons (born before or conceived after the famine) using Cox regression.In total, 500 persons (25.1%) had died after age 18. Women exposed to famine in early gestation had higher overall (HR 1.49, 95% CI 1.00, 2.23), cancer (HR 2.17, 95% CI 1.32,3.58) and cardiovascular mortality (HR 2.33, 95% CI 0.91, 5.95) compared to unexposed women. Mortality rates among men were not different between exposure groups.This study showed that women, but not men, exposed to famine in early gestation had increased overall, cardiovascular and cancer mortality up to age 76. Although prenatal famine exposure affects adult health of both men and women, it seems to only lead to increased mortality among women. [ABSTRACT FROM AUTHOR]

Objective: To address cancer‐specific mortality free‐survival (CSM‐FS) differences in patients with urothelial carcinoma of the urinary bladder (UCUB) vs non‐UCUB who underwent trimodal therapy (TMT), according to organ confined (OC: T2N0M0) vs non‐organ confined (NOC: T3–4NanyM0 or TanyN1–3M0) clinical stages. Patients and Methods: Within the Surveillance, Epidemiology, and End Results database (2004–2020), we identified patients with cT2–T4N0–N3M0 bladder cancer treated with TMT, defined as the combination of transurethral resection of bladder tumour, chemotherapy, and radiotherapy. Temporal trends described TMT use over time. Kaplan–Meier plots and multivariable Cox regression (MCR) models addressed CSM in UCUB vs non‐UCUB according to OC vs NOC stages. Results: Of 5130 assessable TMT‐treated patients, 425 (8%) harboured non‐UCUB vs 4705 (92%) who had UCUB. The TMT rates increased for patients with OC UCUB from 92.4% to 96.8% (estimated annual percentage change of 0.4%, P < 0.001), but not in the NOC stages (P = 0.3). In the OC stage, the median CSM‐FS was 36 months in patients with non‐UCUB vs 60 months in those with UCUB, respectively (P = 0.01). Conversely, in the NOC stage, the median CSM‐FS was 23 months both in UCUB and non‐UCUB (P = 0.9). In the MCR models addressing OC stage, non‐UCUB histology independently predicted higher CSM (hazard ratio 1.45, P = 0.004), but not in the NOC stage (P = 0.9). Conclusion: In OC UCUB, TMT rates have increased over time in a guideline‐consistent fashion. Patients with OC non‐UCUB treated with TMT showed a CSM disadvantage relative to OC UCUB. In the NOC stage, use of TMT resulted in dismal CSM, regardless of UCUB vs non‐UCUB histology. [ABSTRACT FROM AUTHOR]

Income inequality is associated with poor health outcomes, but its association with colorectal cancer is not well-studied. The authors aimed to determine the association between income inequality and colorectal cancer incidence/mortality in U.S. counties, and hypothesized that this association was mediated by deprivation. The authors performed a cross-sectional study of U.S. counties from 2015-2019 using statewide cancer registries and the Centers for Disease Control and Prevention WONDER database. Generalized linear negative binomial regression was performed in 2024 to estimate the association between Gini coefficient (income inequality) and colorectal cancer incidence/mortality using incidence rate ratios (IRRs) for the entire cohort and stratified by rurality. A total of 697,981 colorectal cancer cases were diagnosed in the 5-year study period. On adjusted regression, for every 0.1 higher Gini coefficient, there was an 11% higher risk of both colorectal cancer incidence and mortality (IRR 1.11, 95%CI 1.03,1.19 and IRR 1.11, 95%CI 1.05, 1.18 respectively). The association between income inequality and incidence/mortality peaked in more rural counties, however there was not an overall dose-dependent relationship between rurality and these associations. Deprivation mediated the association between income inequality and colorectal cancer incidence (indirect effect B coefficient 0.088, p<0.001) and mortality (B coefficient 0.088, p<0.001). The magnitude and direction of the direct, indirect, and total effects differed in each rurality strata. Much of income inequality's association with colorectal cancer outcomes operates through deprivation. Rural counties have a stronger association between higher income inequality and higher mortality, which works in tandem with deprivation. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer remains a leading cause of cancer-related mortality worldwide. Detecting mutations in the epidermal growth factor receptor (EGFR) is crucial for treatment selection due to the response to tyrosine kinase inhibitors (TKIs) in these patients. Objective: Describe the prevalence and identify factors associated with survival in stage IV lung cancer patients harboring EGFR mutations in a real-world setting. Materials and methods: A retrospective cohort study was conducted to identify factors associated with progression-free survival (PFS), overall survival (OS) and response rate in stage IV lung cancer patients with EGFR mutations. Results: Data from 771 patients diagnosed with lung cancer between 2017 and 2021 at the Hospital Italiano de Buenos Aires were analysed. The prevalence of EGFR mutations was 18% (139), with a median follow-up of 30 months. Of these, 118 were treated with EGFR TKIs, with a higher objective response rate observed with osimertinib compared to first or second-generation TKIs. Adverse prognostic factors included an ECOG performance status greater than 1, uncommon mutations, high disease burden and the presence of brain or hepatic metastases. Osimertinib was associated with a reduced risk of progression or death, even after adjusting for these prognostic factors. The median PFS was 13 months, with a significant OS difference between patients treated with osimertinib versus first or second-generation inhibitors. Conclusion: This study underscores the importance of EGFR mutation detection in stage IV lung cancer patients and supports the need for personalised therapeutic approaches to improve outcomes in this patient population. [ABSTRACT FROM AUTHOR]

Introduction: Gastric cancer (GC) is the third leading cause of global cancer-related mortality. Despite the shifting burden of GC to low-and middle-income countries, the data regarding incidence, treatment, and outcomes in these settings are sparse. The primary aim of this systematic review was to aggregate all available data on GC in sub-Saharan Africa (SSA) to describe the variability in incidence across the region. Methods: Studies reporting population-based primary data on GC in SSA were considered. The inclusion was limited to primary studies published between January 1995 and March 2022 which comprised of adult patients in SSA with GC. Studies without accessible full text in either French or English language were excluded. Unadjusted GC incidence rates with their standard errors for each study were recalculated from the crude numerators and denominators provided in individual studies. Results: A total of 5,626 articles were identified in the initial search, of which, 69 studies were retained. Reported incidence rates ranged from a high of 5.56 GC cases per 100,000 in Greater Meru Kenya to a low of 0.04 GC cases per 100,000 people in Benin City Nigeria. The overall crude pooled incidence was 1.20 GC cases per 100, 000 (95%CI 1.15-1.26) with a variability of 99.83% (I2 p < 0.001). From the 29 high-quality population- based registry studies the crude pooled incidence was 1.71 GC cases per 100,000 people (95%CI 1.56-21.88) with a variability of 99.60%. Conclusion: This systemic review demonstrates that GC incidence is highly variable across SSA. The limited data on GC treatment, mortality, and survival presents a significant challenge to providing a complete epidemiologic description of the burden of GC in SSA. There is a need for further robust data collection, exploration, and research studies on cancer care in SSA, with continued assessment of primary data availability. [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: The HALP score, comprising hemoglobin, albumin, lymphocyte, and platelet levels, serves as an indicator of both nutritional and inflammatory status. However, its correlation with all-cause and cause-specific mortality among cancer survivors remains unclear. Therefore, this study aims to investigate the relationship between HALP scores and mortality outcomes in this population. Method: We extracted cohort data spanning ten cycles (1999-2018) from the U.S. National Health and Nutrition Examination Survey (NHANES). Mortality rates, determined using the National Death Index (NDI) as of December 31, 2019, were assessed. Weighted multivariate logistic regression analyzed the association between HALP scores and cancer prevalence. Kaplan-Meier analyses and weighted multivariate-adjusted Cox analyses investigated the link between HALP scores and all-cause and cause-specific mortality in cancer survivors. Restricted cubic spline (RCS) analysis was employed to assess nonlinear relationships. Furthermore, multi-parametric subgroup analyses were conducted to ensure the robustness of the results. Results: Our study included 41,231 participants, of whom 3,786 were cancer survivors (prevalence: 9.5%). Over a median follow-up of 91 months (range: 51-136), we observed 1,339 deaths, including 397 from cancer, 368 from cardiocerebrovascular disease, and 105 from respiratory disease. Elevated HALP scores showed a consistent association with reduced cancer incidence (P for trend <0.001). In multivariable-adjusted Cox regression analyses, HALP scores were significantly inversely associated with all-cause mortality, cancer mortality, cardio-cerebrovascular disease mortality, and respiratory disease mortality in cancer survivors (P for trend < 0.05). Nonlinear relationships between HALP scores and all-cause and cause-specific mortality in cancer survivors were evident through RCS regression modeling (P for nonlinearity < 0.01). Kaplan-Meier analyses demonstrated that higher HALP scores were indicative of a poorer prognosis. Conclusion: Our findings indicate a notable inverse correlation between HALP scores and both all-cause and cause-specific mortality among cancer survivors. [ABSTRACT FROM AUTHOR]

Previous studies suggest that Dupuytren's disease is associated with increased mortality, but most studies failed to account for important confounders. In this population-based cohort study, general practitioners' (GP) data were linked to Statistics Netherlands to register all-cause and disease-specific mortality. Patients with Dupuytren's disease were identified using the corresponding diagnosis code and assessing free-text fields from GP consultations. Multiple imputations were performed to estimate missing values of covariates, followed by 1:7 propensity score matching to balance cases with controls on confounding factors. A frailty proportional hazard model was used to compare mortality between both groups. Out of 209,966 individuals, 2561 patients with Dupuytren's disease were identified and matched to at least four controls. After a median follow-up of 5 years, mortality was found to be actually reduced in patients with Dupuytren's disease. There was no difference in mortality secondary to cancer or cardiovascular disease. Future studies with longer average follow-up using longitudinal data should clarify these associations in the longer term. Level of evidence: III [ABSTRACT FROM AUTHOR]

Context Patients with diabetes are at increased risk of dying from liver-related events, but little is known on whether this increased risk has changed in recent years. Objective The aim of the present study is to describe time trends in cause-specific liver-related mortality in people with and without diabetes from the general Italian population. Methods Data were retrieved from the health care utilization databases of Lombardy, a region of Italy that accounts for about 16% (almost 10 million) of its population. Annual cause-specific mortality rates and proportionate mortality were computed among individuals with and without diabetes from 2010 to 2019. Liver-related deaths were categorized as viral, alcohol related, and nonviral nonalcohol related (NVNA). Results Liver diseases were responsible for 2% and 1% of deaths in people with and without diabetes (2019). Among patients with diabetes, the crude mortality rate for liver diseases decreased from 1.13 to 0.64 deaths per 1000 person-years from 2010 to 2019. The largest proportion of liver-related deaths was attributable to NVNA diseases and it increased from 63% in 2010 to 68% in 2019, with a corresponding relative reduction of viral causes (from 27% to 23%). The standardized mortality ratio for patients with diabetes was 3.35 (95% CI 2.96-3.76) for NVNA, 1.66 (95% CI 1.33-2.01) for viral hepatitis, and 1.61 (95% CI 1.13-2.17) for alcoholic liver disease and it remained relatively stable over time. Excess mortality risk in patients with diabetes for liver-related mortality was higher than for cardiovascular mortality and cancer. Conclusion While liver-related mortality rates decreased significantly among patients with diabetes, NVNA causes made up the majority of cases. Excess mortality for liver-related causes in patients with diabetes compared with controls remained constant in the studied period. [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]

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: Inflammation plays a crucial role in prostate cancer (PCa) progression and mortality. This study aimed to investigate the predictive value of the inflammatory burden index (IBI) and its components for mortality risk among men aged 40 years and older. Methods: A total of 7,344 participants from the NHANES 2001–2010 were included. High PCa risk was defined as a %fPSA greater than 25% and a tPSA level less than 4.0 ng/mL. Cox regression and logistic regression analyses were conducted to assess the association between IBI, PCa risk, and mortality. Receiver operating characteristic (ROC) curve analysis and random survival forest (RSF) model were utilized to evaluate the predictive value of IBI and its components for mortality. Results: Elevated IBI levels were significantly associated with an increased risk of all-cause mortality (HR = 1.08 [1.05–1.10]) and cancer mortality (HR = 1.11 [1.07–1.15]). High-risk PCa cases also exhibited elevated mortality risk (all-cause: HR = 1.35 [1.19–1.54]; cancer: HR = 1.65 [1.27–2.14]). Additionally, the combined effect of elevated IBI levels and high PCa risk showed a synergistic impact on mortality outcomes (all-cause: HR = 1.49 [1.27–1.74]; cancer: HR = 1.76 [1.29–2.40]). ROC curve analysis revealed that IBI had the highest AUC for predicting all-cause mortality (AUC = 0.690 at 3 years, 0.622 at 5 years, 0.634 at 10 years, and 0.632 at 15 years) compared to its individual components (CRP, NEU, LYM). RSF analysis highlighted IBI as the most significant predictor of all-cause and cancer mortality. Conclusion: The combined effect of elevated IBI levels and high PCa risk demonstrated a synergistic impact on increased mortality risk among men aged 40 years and older. IBI demonstrated superior predictive performance for mortality outcomes compared to individual inflammatory markers. These findings underscore the potential utility of IBI as a prognostic biomarker for mortality risk assessment in individual with high PCa risk. [ABSTRACT FROM AUTHOR]