PPIH acts as a potential predictive biomarker for patients with common solid tumors.

BACKGROUND: Our previous studies have indicated that mRNA and protein levels of PPIH are significantly upregulated in Hepatocellular Carcinoma (LIHC) and could act as predictive biomarkers for patients with LIHC. Nonetheless, the expression and implications of PPIH in the etiology and progression of common solid tumors have yet to be explored, including its potential as a serum tumor marker. METHODS: We employed bioinformatics analyses, augmented with clinical sample evaluations, to investigate the mRNA and protein expression and gene regulation networks of PPIH in various solid tumors. We also assessed the association between PPIH expression and overall survival (OS) in cancer patients using Kaplan-Meier analysis with TCGA database information. Furthermore, we evaluated the feasibility and diagnostic efficacy of PPIH as a serum marker by integrating serological studies with established clinical tumor markers. RESULTS: Through pan-cancer analysis, we found that the expression levels of PPIH mRNA in multiple tumors were significantly different from those in normal tissues. This study is the first to report that PPIH mRNA and protein levels are markedly elevated in LIHC, Colon adenocarcinoma (COAD), and Breast cancer (BC), and are associated with a worse prognosis in these cancer patients. Conversely, serum PPIH levels are decreased in patients with these tumors (LIHC, COAD, BC, gastric cancer), and when combined with traditional tumor markers, offer enhanced sensitivity and specificity for diagnosis. CONCLUSION: Our findings propose that PPIH may serve as a valuable predictive biomarker in tumor patients, and its secreted protein could be a potential serum marker, providing insights into the role of PPIH in cancer development and progression.

Heavy Lifetime Cannabis Use and Mortality by Sex.

Importance: The association between mortality and cannabis use remains unclear. Objective: To examine sex-stratified associations of cumulative lifetime cannabis use with all-cause, cardiovascular disease (CVD), and cancer mortality in the UK Biobank population. Design, Setting, and Participants: This cohort study used data from volunteers in the UK Biobank population. Participant monitoring for mortality in the UK Biobank study commenced from the point of their inclusion between 2006 and 2010 and continued until December 19, 2020. Data regarding the causes of death were sourced from the National Health Service Information Centre. Data were analyzed from inception of study inclusion to December 2020. Exposure: Cannabis use status was assessed by questionnaire and categorized as heavy, moderate, low, and never. Main Outcomes and Measures: The main outcomes were all-cause, CVD, and cancer mortality. Sex-stratified associations of cumulative lifetime cannabis use with mortality were estimated using Cox proportional hazards regression with adjustment for demographic and clinical variables. Results: Among 121 895 participants (54.51% females with mean [SD] age of 55.15 [7.64] years; 45.49% males with mean [SD] age of 56.46 [7.79] years) during an overall median of 11.80 years (IQR, 10.53-13.22 years) of follow-up, 2375 total deaths occurred, including 1411 deaths from CVD and 440 from cancer. In males, after full adjustment, the hazard ratios (HRs) were 1.28 (95% CI, 0.90-1.81) for all-cause mortality, 0.98 (95% CI, 0.43-2.25) for CVD mortality, and 1.09 (95% CI, 0.71-1.67) for cancer mortality among heavy cannabis users compared with never users. In females, after full adjustment, the HRs were 1.49 (95% CI, 0.92-2.40) for all-cause mortality, 2.67 (95% CI, 1.19-4.32) for CVD mortality, and 1.61 (95% CI, 0.91-2.83) for cancer mortality among heavy cannabis users compared with never users. In female current tobacco users, after full adjustment, heavy cannabis use was associated with all-cause mortality (HR, 2.25; 95% CI, 1.12-4.53), CVD mortality (HR, 2.56; 95% CI, 1.43-15.36), and cancer mortality (HR, 3.52; 95% CI, 1.50-8.33) and among never tobacco users was associated with CVD mortality (HR, 2.98; 95% CI, 1.67-6.61). In male current tobacco users, heavy cannabis use was associated with cancer mortality (HR, 2.44; 95% CI, 1.14-5.23). Conclusions and Relevance: In this study, a positive association between CVD mortality and heavy lifetime cannabis use was observed among females. Longitudinal studies are needed in general populations to investigate the potential effects of cannabis on mortality.

The Naples prognostic score serves as a predictor and prognostic indicator for cancer survivors in the community.

OBJECTIVE: Inflammation, malnutrition, and cancer are intricately interconnected. Despite this, only a few studies have delved into the relationship between inflammatory malnutrition and the risk of death among cancer survivors. This study aimed to specifically investigate the association between the categorically defined Naples prognostic score (NPS) and the prognosis of cancer survivors. METHODS: Data from 42,582 participants in the National Health and Nutrition Examination Survey (NHANES, 1999-2018) were subjected to analysis. Naples prognostic scores (NPS) were computed based on serum albumin (ALB), total cholesterol (TC), neutrophil to lymphocyte ratio (NLR), and lymphocyte to monocyte ratio (LMR), and participants were stratified into three groups accordingly. Cancer status was ascertained through a self-administered questionnaire, while mortality data were sourced from the National Death Index up to December 31, 2019. Multiple logistic regression was employed to estimate the odds ratio (OR) with a 95% confidence interval (CI) between NPS and cancer prevalence within the U.S. community population. Kaplan-Meier survival analysis and the Log-rank test were utilized to compare survival disparities among the three groups. Additionally, Cox proportional regression was utilized to estimate the hazard ratio (HR) with a 95% CI. RESULTS: The incidence of cancers was 9.86%. Among the participants, 8140 individuals (19.1%) were classified into Group 0 (NPS 0), 29,433 participants (69.1%) into Group 1 (NPS 1 or 2), and 5009 participants (11.8%) into Group 2 (NPS 3 or 4). After adjusting for confounding factors, the cancer prevalence for the highest NPS score yielded an odds ratio (OR) of 1.64 (95% CI: 1.36, 1.97) (P(for trend) < 0.05). In comparison to cancer survivors in Group 0, those with the highest NPS had adjusted hazard ratios (HRs) of 2.57 (95% CI: 1.73, 3.84) for all-cause mortality, 3.44 (95% CI: 1.64, 7.21) for cardiovascular mortality, 1.60 (95% CI: 1.01, 2.56) for cancer mortality, and 3.15 (95% CI: 1.74, 5.69) for other causes of mortality (All P(for trend) < 0.05). These associations remained consistent when stratified by age, sex, race, and body mass index. CONCLUSIONS: This study indicates that the Naples prognostic score (NPS), serving as a novel prognostic metric integrating inflammation and nutritional status, is closely linked to cancer prognosis within the general population.

Association of depressive symptoms and sleep disturbances with survival among US adult cancer survivors.

BACKGROUND: Depression and sleep disturbances are associated with increased risks of various diseases and mortality, but their impacts on mortality in cancer survivors remain unclear. The objective of this study was to characterize the independent and joint associations of depressive symptoms and sleep disturbances with mortality outcomes in cancer survivors. METHODS: This population-based prospective cohort study included cancer survivors aged ≥ 20 years (n = 2947; weighted population, 21,003,811) from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 cycles. Depressive symptoms and sleep disturbances were self-reported. Depressive symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9). Death outcomes were determined by correlation with National Death Index records through December 31, 2019. Primary outcomes included all-cause, cancer-specific, and noncancer mortality. RESULTS: During the median follow-up of 69 months (interquartile range, 37-109 months), 686 deaths occurred: 240 participants died from cancer, 146 from heart disease, and 300 from other causes. Separate analyses revealed that compared with a PHQ-9 score (0-4), a PHQ-9 score (5-9) was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.28; 95% CI, 1.03-1.59), and a PHQ-9 score (≥ 10) was associated with greater risk of all-cause mortality (HR, 1.37; 95% CI, 1.04-1.80) and noncancer mortality (HR, 1.45; 95% CI, 1.01-2.10). Single sleep disturbances were not associated with mortality risk. In joint analyses, the combination of a PHQ-9 score ≥ 5 and no sleep disturbances, but not sleep disturbances, was associated with increased risks of all-cause mortality, cancer-specific mortality, and noncancer mortality. Specifically, compared with individuals with a PHQ-9 score of 0-4 and no sleep disturbances, HRs for all-cause mortality and noncancer mortality in individuals with a PHQ-9 score of 5-9 and no sleep disturbances were 1.72 (1.21-2.44) and 1.69 (1.10-2.61), respectively, and 2.61 (1.43-4.78) and 2.77 (1.27-6.07), respectively, in individuals with a PHQ-9 score ≥ 10 and no sleep disturbances; HRs for cancer-specific mortality in individuals with a PHQ-9 score ≥ 5 and no sleep disturbances were 1.95 (1.16-3.27). CONCLUSIONS: Depressive symptoms were linked to a high risk of mortality in cancer survivors. The combination of a PHQ-9 score (≥ 5) and an absence of self-perceived sleep disturbances was associated with greater all-cause mortality, cancer-specific mortality, and noncancer mortality risks, particularly in individuals with a PHQ-9 score (≥ 10).

A randomized control trial to compare mortality in recipients of leucoreduced and non-leucoreduced whole blood transfusion in patients with cancer in Uganda.

BACKGROUND: Mortality benefit of transfusion with leucoreduced whole blood has not been demonstrated in the sub-Saharan Africa (SSA). We compared mortality in patients with cancer transfused with leucoreduced and non-leucoreduced whole blood in a SSA setting. METHODS: An open-label randomized controlled trial was conducted at the Uganda Cancer Institute where participants were randomized in a 1:1 ratio into the leucoreduced and non-leucoreduced whole blood transfusion arms. Leucocyte filtration of whole blood was performed within 72 h of blood collection. Patients aged ≥ 15 years who were prescribed blood transfusion by the primary physicians were eligible for study enrolment. Mortality difference was analyzed using intention-to-treat survival analysis and cox proportional hazard model was used to analyze factors associated with mortality. RESULTS: There were 137 participants randomized to the leucoreduced and 140 to the non-leucoreduced arms. Baseline characteristics were similar between the two arms. The median number of blood transfusions received was 1 (IQR, 1-3) unit and 2 (IQR, 1-3) units in the leucoreduced and non-leucoreduced arms respectively, p = 0.07. The 30-day mortality rate in the leucoreduced arm was 4.6% (95% CI, 2.1-10) and was 6.2% (95% CI, 3.2-12.1) in the non-leucoreduced arm (p = 0.57), representing an absolute effect size of only 1.6%. Increasing age (HR = 0.92, 95% CI, 0.86-0.98, p = 0.02) and Eastern Co-operative Oncology Group (ECOG) performance score of 1 (HR = 0.03, 95% CI, 0.00-0.31, p < 0.01) were associated with reduced 30-day mortality. CONCLUSIONS: The study failed to demonstrate mortality difference between cancer patients transfused with leucoreduced and non-leucoreduced whole blood. Although this study does not support nor refute universal leucoreduction to reduce mortality in patients with cancer in SSA, it demonstrates the feasibility of doing transfusion RCTs in Uganda, where a multi-center trial with an appropriate sample size is needed. TRIAL REGISTRATION: Pan African Clinical Trial Registry, https://pactr.samrc.ac.za/ (PACTR202302787440132). Registered on 06/02/2023.

Weight training and risk of all-cause, cardiovascular disease and cancer mortality among older adults.

BACKGROUND: While previous studies indicate muscle-strengthening exercises may reduce mortality risk, further research is needed to increase certainty of the evidence. We investigated overall and dose-response associations between weight training and the risks of all-cause, cardiovascular disease (CVD) and cancer mortality in a large cohort of older adults with long follow-up time and a large number of deaths. We also investigated the joint associations of weight training and aerobic exercise with mortality risk. METHODS: Weight training was assessed via self-report in 2004-05 in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study (USA; n = 216 339), with follow-up to 2019. Cox regression estimated the hazard ratios (HR) and 95% confidence intervals (CI) for the associations between weight training and mortality, after adjusting for confounders including aerobic exercise. RESULTS: Around 25% of participants [mean age = 69.9 years (standard deviation = 5.4), 58% men] reported engaging in weight training over the past year, and there were 79 107 (37%) deaths. Engaging in any weight training (vs none) was associated with lower risks of all-cause (HR = 0.94; 95% CI = 0.93-0.96), CVD (HR = 0.92; 95% CI = 0.90-0.95) and cancer mortality (HR = 0.95; 95% CI = 0.92-0.98). More time spent in weight training was associated with only marginally greater risk reductions. Larger risk reductions were observed among women than men. Performing both aerobic exercise and weight training conferred the greatest mortality risk reduction; weight training was not associated with mortality risk among participants who did no aerobic exercise. CONCLUSION: Performing any amount of weight training lowered mortality risk.

Ambient air pollution as a time-varying covariate in the survival probability of childhood cancer patients in the upper Northern Thailand.

The objective of this study is to determine the possible association between exposure to air pollution and the risk of death from cancer during childhood in upper northern Thailand. Data were collected on children aged 0-15 years old diagnosed with cancer between January 2003 and December 2018 from the Chiang Mai Cancer Registry. Survival rates were determined by using Kaplan-Meier curves. Cox proportional hazard models were used to investigate associations of potential risk factors with the time-varying air pollution level on the risk of death. Of the 540 children with hematologic cancer, 199 died from any cause (overall mortality rate = 5.3 per 100 Person-Years of Follow-Up (PYFU); 95%CI = 4.6-6.0). Those aged less than one year old (adjusted hazard ratio [aHR] = 2.07; 95%CI = 1.25-3.45) or ten years old or more (aHR = 1.41; 95%CI = 1.04-1.91) at the time of diagnosis had a higher risk of death than those aged one to ten years old. Those diagnosed between 2003 and 2013 had an increased risk of death (aHR = 1.65; 95%CI = 1.13-2.42). Of the 499 children with solid tumors, 214 died from any cause (5.9 per 100 PYFU; 95%CI = 5.1-6.7). Only the cancer stage remained in the final model, with the metastatic cancer stage (HR = 2.26; 95%CI = 1.60-3.21) and the regional cancer stage (HR = 1.53; 95%CI = 1.07-2.19) both associated with an increased risk of death. No association was found between air pollution exposure and all-cause mortality for either type of cancer. A larger-scale analytical study might uncover such relationships.

Trends in incidence and survival of childhood cancers in Khon Kaen, Thailand (2000-2019): a population-based Khon Kaen Cancer Registry study.

BACKGROUND: In Thailand, the national health care system and nationwide standard treatment protocols have evolved over time, potentially influencing the trends in the incidence and survival rates of childhood cancers. However, further investigations are required to comprehensively study these trends in Khon Kaen, Thailand. METHODS: Childhood cancer patients aged 0-14 years (n = 541) who were diagnosed with one of the five most common cancers between 2000 and 2019 from the population-based Khon Kaen Cancer Registry were enrolled. Descriptive statistics were used to analyse the demographic data, which are presented as numbers, percentages, means, and standard deviations. The trends in incidence between 2000 and 2019, including age-standardized incidence rates (ASRs) and annual percent changes (APCs), were analysed using the Joinpoint regression model. Survival analysis was performed for 5-year relative survival rates (RSRs) according to the Pohar Perme estimator and Kaplan-Meier survival curves. RESULTS: The ASRs of the overall top 5 childhood cancer groups were 67.96 and 106.12 per million person-years in 2000 and 2019, respectively. Overall, the APC significantly increased by 2.37% each year for both sexes. The overall 5-year RSRs were 60.5% for both sexes, 58.2% for males, and 63.9% for females. The highest 5-year RSR was for germ cell tumours (84.3%), whereas the lowest 5-year RSR was for neuroblastoma (29.1%). CONCLUSIONS: The incidence and survival rates of childhood cancers in Khon Kaen, Thailand, varied according to sex. The incidence trends increased over time, meanwhile, the relative survival rates rose to satisfactory levels and were comparable to those of other nations with similar financial status. The implementation of national health policies and adherence to national treatment guidelines have improved cancer diagnosis and treatment outcomes.

PESSA: A web tool for pathway enrichment score-based survival analysis in cancer.

The activation levels of biologically significant gene sets are emerging tumor molecular markers and play an irreplaceable role in the tumor research field; however, web-based tools for prognostic analyses using it as a tumor molecular marker remain scarce. We developed a web-based tool PESSA for survival analysis using gene set activation levels. All data analyses were implemented via R. Activation levels of The Molecular Signatures Database (MSigDB) gene sets were assessed using the single sample gene set enrichment analysis (ssGSEA) method based on data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), The European Genome-phenome Archive (EGA) and supplementary tables of articles. PESSA was used to perform median and optimal cut-off dichotomous grouping of ssGSEA scores for each dataset, relying on the survival and survminer packages for survival analysis and visualisation. PESSA is an open-access web tool for visualizing the results of tumor prognostic analyses using gene set activation levels. A total of 238 datasets from the GEO, TCGA, EGA, and supplementary tables of articles; covering 51 cancer types and 13 survival outcome types; and 13,434 tumor-related gene sets are obtained from MSigDB for pre-grouping. Users can obtain the results, including Kaplan-Meier analyses based on the median and optimal cut-off values and accompanying visualization plots and the Cox regression analyses of dichotomous and continuous variables, by selecting the gene set markers of interest. PESSA (https://smuonco.shinyapps.io/PESSA/ OR http://robinl-lab.com/PESSA) is a large-scale web-based tumor survival analysis tool covering a large amount of data that creatively uses predefined gene set activation levels as molecular markers of tumors.

Cancer incidence, treatment, and survival in the prison population compared with the general population in England: a population-based, matched cohort study.

BACKGROUND: The growing and ageing prison population in England makes accurate cancer data of increasing importance for prison health policies. This study aimed to compare cancer incidence, treatment, and survival between patients diagnosed in prison and the general population. METHODS: In this population-based, matched cohort study, we used cancer registration data from the National Cancer Registration and Analysis Service in England to identify primary invasive cancers and cervical cancers in situ diagnosed in adults (aged ≥18 years) in the prison and general populations between Jan 1, 1998, and Dec 31, 2017. Ministry of Justice and Office for National Statistics population data for England were used to calculate age-standardised incidence rates (ASIR) per year and age-standardised incidence rate ratios (ASIRR) for the 20-year period. Patients diagnosed with primary invasive cancers (ie, excluding cervical cancers in situ) in prison between Jan 1, 2012, and Dec 31, 2017 were matched to individuals from the general population and linked to hospital and treatment datasets. Matching was done in a 1:5 ratio according to 5-year age group, gender, diagnosis year, cancer site, and disease stage. Our primary objectives were to compare the incidence of cancer (1998-2017); the receipt of treatment with curative intent (2012-17 matched cohort), using logistic regression adjusted for matching variables (excluding cancer site) and route to diagnosis; and overall survival following cancer diagnosis (2012-17 matched cohort), using a Cox proportional hazards model adjusted for matching variables (excluding cancer site) and route to diagnosis, with stratification for the receipt of any treatment with curative intent. FINDINGS: We identified 2015 incident cancers among 1964 adults (1556 [77·2%] men and 459 [22·8%] women) in English prisons in the 20-year period up to Dec 31, 2017. The ASIR for cancer for men in prison was initially lower than for men in the general population (in 1998, ASIR 119·33 per 100 000 person-years [95% CI 48·59-219·16] vs 746·97 per 100 000 person-years [742·31-751·66]), but increased to a similar level towards the end of the study period (in 2017, 856·85 per 100 000 person-years [675·12-1060·44] vs 788·59 per 100 000 person-years [784·62-792·57]). For women, the invasive cancer incidence rate was low and so ASIR was not reported for this group. Over the 20-year period, the incidence of invasive cancer for men in prison increased (incidence rate ratio per year, 1·05 [95% CI 1·04-1·06], during 1999-2017 compared with 1998). ASIRRs showed that over the 20-year period, overall cancer incidence was lower in men in prison than in men in the general population (ASIRR 0·76 [95% CI 0·73-0·80]). The difference was not statistically significant for women (ASIRR 0·83 [0·68-1·00]). Between Jan 1, 2012, and Dec 31, 2017, patients diagnosed in prison were less likely to undergo curative treatment than matched patients in the general population (274 [32·3%] of 847 patients vs 1728 [41·5%] of 4165; adjusted odds ratio (OR) 0·72 [95% CI 0·60-0·85]). Being diagnosed in prison was associated with a significantly increased risk of death on adjustment for matching variables (347 deaths during 2021·9 person-years in the prison cohort vs 1626 deaths during 10 944·2 person-years in the general population; adjusted HR 1·16 [95% CI 1·03-1·30]); this association was partly explained by stratification by curative treatment and further adjustment for diagnosis route (adjusted HR 1·05 [0·93-1·18]). INTERPRETATION: Cancer incidence increased in people in prisons in England between 1998 and 2017, with patients in prison less likely to receive curative treatments and having lower overall survival than the general population. The association with survival was partly explained by accounting for differences in receipt of curative treatment and adjustment for diagnosis route. Improved routine cancer surveillance is needed to inform prison cancer policies and decrease inequalities for this under-researched population. FUNDING: UK National Institute for Health and Care Research, King's College London, and Strategic Priorities Fund 2019/20 of Research England via the University of Surrey.

Assessing patient risk, benefit, and outcomes in drug development: A decade of ramucirumab clinical trials.

OBJECTIVE: This study aims to evaluate published clinical trials of ramucirumab to assess the risk/benefit profile and burden over time for patients. BACKGROUND: The burden of oncologic drug development on patients paired with increasing clinical trial failure rates emphasizes the need for reform of drug development. Identifying and addressing patterns of excess burden can guide policy, ensure evidence-based protections for trial participants, and improve medical decision-making. METHODS: On May 25, 2023 a literature search was performed on Pubmed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov for clinical trials using ramucirumab as monotherapy or in combination with other interventions for cancer treatment. Authors screened titles and abstracts for potential inclusion in a masked, duplicate fashion. Following data screening, data was extracted in a masked, duplicate fashion. Trials were classified as positive when meeting their primary endpoint and safety, negative or indeterminate. RESULTS: Ramucirumab was initially approved for gastric cancer but has since been tested in 20 cancers outside of its FDA approved indications. In our analysis of ramucirumab trials, there were a total of 10,936 participants and 10,303 adverse events reported. Gains in overall survival and progression-free survival for patients were 1.5 and 1.2 months, respectively. FDA-approved indications have reported more positive outcomes in comparison to off-label indications. CONCLUSION: We found that FDA-approved indications for ramucirumab had better efficacy outcomes than non-approved indications. However, a concerning number of adverse events were observed across all trials assessed. Participants in ramucirumab randomized controlled trials saw meager gains in overall survival when evaluated against a comparison group. Clinicians should carefully weigh the risks associated with ramucirumab therapy given its toxicity burden and poor survival gains.

Associations of serum vitamin B6 status with the risks of cardiovascular, cancer, and all-cause mortality in the elderly.

Background: There are few studies investigating the relationship between serum vitamin B6 and mortality risk in the elderly. This study hereby evaluated the associations between biomarkers of serum vitamin B6 status and cardiovascular, cancer, and all-cause mortality risks in the elderly. Methods: Our study included a total of 4,881 participants aged 60 years or older from the National Health and Nutrition Examination Survey (NHANES) 2005-2010. Serum vitamin B6 status was estimated based on levels of pyridoxal 5'-phosphate (PLP), 4-pyridoxic acid (4-PA), and vitamin B6 turnover rate (4-PA/PLP) detected by high-performance liquid chromatography. Survival status and corresponding causes of death were matched through the National Death Index records through December 31, 2019. Multivariate Cox regression model was adopted to assess the relationships between serum vitamin B6 status and the risk of mortality. Results: During a median follow-up period of 10.33 years, 507 cardiovascular deaths, 426 cancer deaths, and 1995 all-cause deaths were recorded, respectively. In the multivariate-adjusted Cox model, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the highest versus the lowest quartiles of PLP, 4-PA, and 4-PA/PLP were 0.70(0.54-0.90), 1.33(0.88-2.02), and 2.01(1.41-2.79) for cardiovascular mortality, 0.73(0.52-1.02), 1.05(0.71-1.57), and 1.95(1.25-3.05) for cancer mortality, and 0.62(0.53-0.74), 1.05(0.82-1.34), and 2.29(1.87-2.79) for all-cause mortality, respectively. Conclusion: Our study found that lower serum PLP levels were associated with increased risks of cardiovascular and all-cause mortality among the elderly population. And higher vitamin B6 turnover rate was associated with increased risks of cardiovascular, cancer, and all-cause mortality.

A novel non-negative Bayesian stacking modeling method for Cancer survival prediction using high-dimensional omics data.

BACKGROUND: Survival prediction using high-dimensional molecular data is a hot topic in the field of genomics and precision medicine, especially for cancer studies. Considering that carcinogenesis has a pathway-based pathogenesis, developing models using such group structures is a closer mimic of disease progression and prognosis. Many approaches can be used to integrate group information; however, most of them are single-model methods, which may account for unstable prediction. METHODS: We introduced a novel survival stacking method that modeled using group structure information to improve the robustness of cancer survival prediction in the context of high-dimensional omics data. With a super learner, survival stacking combines the prediction from multiple sub-models that are independently trained using the features in pre-grouped biological pathways. In addition to a non-negative linear combination of sub-models, we extended the super learner to non-negative Bayesian hierarchical generalized linear model and artificial neural network. We compared the proposed modeling strategy with the widely used survival penalized method Lasso Cox and several group penalized methods, e.g., group Lasso Cox, via simulation study and real-world data application. RESULTS: The proposed survival stacking method showed superior and robust performance in terms of discrimination compared with single-model methods in case of high-noise simulated data and real-world data. The non-negative Bayesian stacking method can identify important biological signal pathways and genes that are associated with the prognosis of cancer. CONCLUSIONS: This study proposed a novel survival stacking strategy incorporating biological group information into the cancer prognosis models. Additionally, this study extended the super learner to non-negative Bayesian model and ANN, enriching the combination of sub-models. The proposed Bayesian stacking strategy exhibited favorable properties in the prediction and interpretation of complex survival data, which may aid in discovering cancer targets.

Dietary choline intake and health outcomes in U.S. adults: exploring the impact on cardiovascular disease, cancer prevalence, and all-cause mortality.

BACKGROUND: Choline, an indispensable nutrient, plays a pivotal role in various physiological processes. The available evidence regarding the nexus between dietary choline intake and health outcomes, encompassing cardiovascular disease (CVD), cancer, and all-cause mortality, is limited and inconclusive. This study aimed to comprehensively explore the relationship between dietary choline intake and the aforementioned health outcomes in adults aged > 20 years in the U.S. METHODS: This study utilized data from the National Health and Nutrition Examination Survey between 2011 and 2018. Dietary choline intake was evaluated using two 24-h dietary recall interviews. CVD and cancer status were determined through a combination of standardized medical status questionnaires and self-reported physician diagnoses. Mortality data were gathered from publicly available longitudinal Medicare and mortality records. The study utilized survey-weighted logistic and Cox regression analyses to explore the associations between choline consumption and health outcomes. Restricted cubic spline (RCS) analysis was used for dose‒response estimation and for testing for nonlinear associations. RESULTS: In our study of 14,289 participants (mean age 48.08 years, 47.71% male), compared with those in the lowest quintile (Q1), the adjusted odds ratios (ORs) of CVD risk in the fourth (Q4) and fifth (Q5) quintiles of choline intake were 0.70 (95% CI 0.52, 0.95) and 0.65 (95% CI 0.47, 0.90), respectively (p for trend = 0.017). Each 100 mg increase in choline intake was associated with a 9% reduced risk of CVD. RCS analysis revealed a linear correlation between choline intake and CVD risk. Moderate choline intake (Q3) was associated with a reduced risk of mortality, with an HR of 0.75 (95% CI 0.60-0.94) compared with Q1. RCS analysis demonstrated a significant nonlinear association between choline intake and all-cause mortality (P for nonlinearity = 0.025). The overall cancer prevalence association was nonsignificant, except for colon cancer, where each 100 mg increase in choline intake indicated a 23% reduced risk. CONCLUSION: Elevated choline intake demonstrates an inverse association with CVD and colon cancer, while moderate consumption exhibits a correlated reduction in mortality. Additional comprehensive investigations are warranted to elucidate the broader health implications of choline.

Treatment-related mortality among children with cancer in Denmark during 2001-2021.

BACKGROUND: Survival of children with cancer has markedly improved over recent decades, largely due to intensified treatment regimes. The intensive treatment may, however, result in fatal complications. In this retrospective cohort study, we assessed temporal variation in the incidence of treatment-related death and associated risk factors among children diagnosed with cancer in Denmark during 2001-2021. METHOD: Among all children diagnosed with first incident cancer before age 15 years recorded in the Danish Childhood Cancer Register (n = 3,255), we estimated cumulative incidence of treatment-related death (death in the absence of progressive cancer) within 5 years from diagnosis using Aalen-Johansen estimators and assessed associated risk factors using Cox regression. RESULTS: Among all 3,255 children with cancer, 93 (20% of all 459 deaths) died from treatment. Of these treatment-related deaths, 39 (42%) occurred within 3 months of diagnosis. The 5-year cumulative incidences of treatment-related death were 3.3% during 2001-2010 and 2.5% during 2011-2021 (p = 0.20). During 2011-2021, treatment-related deaths accounted for more than half of all deaths among children with haematological cancers. Risk factors varied according to cancer group and included female sex, age below 1 year at diagnosis, disease relapse, stem cell transplantation, central nervous system involvement, and metastasis at diagnosis. INTERPRETATION: Despite increasing treatment intensities, the incidence of treatment-related death has remained stable during the past 20 years in Denmark. Still, clinical attention is warranted to prevent treatment-related deaths, particularly among children with haematological cancers. Patient characteristics associated with increased treatment-related death risk support patient-specific treatment approaches to avoid these fatalities.

Anticancer therapy at end-of-life: A retrospective cohort study.

BACKGROUND: A significant proportion of patients with incurable cancer receive systemic anticancer therapy (SACT) within their last 30 days of life (DOL). The treatment has questionable benefit, nevertheless is considered a quality indicator of end-of-life (EOL) care. This retrospective cohort study aims to investigate the rates and potential predictors of SACT and factors associated with SACT within the last 30 DOL. The study also evaluates the scope of Eastern Cooperative Oncology Group (ECOG) performance status and the modified Glasgow prognostic score (mGPS) as decision-making tools for oncologists. PATIENTS AND MATERIAL: This review of medical records included 383 patients with non-curable cancer who died between July 2018 and December 2019. Descriptive statistics with Chi-squared tests and regression analysis were used to identify factors associated with SACT within the last 30 DOL. RESULTS: Fifty-seven (15%) patients received SACT within the last 30 DOL. SACT within 30 last DOL was associated with shorter time from diagnosis until death (median 234 days vs. 482, p = 0.008) and ECOG score < 3 30 days prior to death (p = 0.001). Patients receiving SACT during the last 30 DOL were more likely to be hospitalised and die in hospital. ECOG and mGPS score were stated at start last line of treatment only in 139 (51%) and 135 (49%) respectively. INTERPRETATION: Those with short time since diagnosis tended to receive SACT more frequently the last 30 DOL. The use of mGPS as a decision-making tool is modest, and there is lack in documentation of performance status.

Evaluating the efficacy and safety of nivolumab and ipilimumab combination therapy compared to nivolumab monotherapy in advanced cancers (excluding melanoma): a systemic review and meta-analysis.

BACKGROUND: Nivolumab (Nivo) and ipilimumab (Ipi) have revolutionized cancer treatment by targeting different pathways. Their combination shows promising results in various cancers, including melanoma, but not all studies have demonstrated significant benefits. A meta-analysis was performed to assess the effectiveness and safety of Nivo-Ipi compared to Nivo alone in advanced cancer types (excluding melanoma). METHODS: Following PRISMA guidelines, we conducted a meta-analysis up to September 30, 2023, searching databases for randomized controlled trials (RCTs). We focused on advanced solid malignancies (excluding melanoma) with specific Nivo and Ipi dosing. Primary outcomes were overall survival (OS), progression-free survival (PFS), grades 3-4 adverse events (AEs), and treatment-related discontinuations. Secondary outcomes included specific adverse events. Statistical analysis in Review Manager included hazard ratio (HR) and risk ratio (RR), assessing heterogeneity (Higgins I2). RESULTS: Nine RCTs, involving 2152 patients covering various malignancies, were analyzed. The Nivo plus Ipi group exhibited a median OS of 12.3 months and a median PFS of 3.73 months, compared to monotherapy with 11.67 months and 3.98 months, respectively. OS showed no significant difference between Nivo and Ipi combination and Nivo alone (HR = 0.97, 95% CI: 0.88 to 1.08, p = 0.61). PFS had a slight improvement with combination therapy (HR = 0.91, 95% CI: 0.82 to 1.00, p = 0.04). Treatment-related cumulative grades 3-4 adverse events were higher with Nivo and Ipi (RR = 1.52, 95% CI: 1.30 to 1.78, p < 0.00001), as were treatment-related discontinuations (RR = 1.99, 95% CI: 1.46 to 2.70, p < 0.0001). Hepatotoxicity (RR = 2.42, 95% CI: 1.39 to 4.24, p = 0.002), GI toxicity (RR = 2.84, 95% CI: 1.44 to 5.59, p = 0.002), pneumonitis (RR = 2.29, 95% CI: 1.24 to 2.23, p = 0.008), dermatitis (RR = 2.96, 95% CI: 1.08 to 8.14, p = 0.04), and endocrine dysfunction (RR = 6.22, 95% CI: 2.31 to 16.71, p = 0.0003) were more frequent with Nivo and Ipi. CONCLUSIONS: Combining nivolumab and ipilimumab did not significantly improve overall survival compared to nivolumab alone in advanced cancers (except melanoma). However, it did show slightly better PFS at the cost of increased toxicity, particularly grades 3-4 adverse events. Specific AEs occurred more frequently in the combination group. Further trials are needed to fully assess this combination in treating advanced cancers.

Development and psychometric evaluation of the death risk perception scale for advanced cancer patients.

BACKGROUND: An accurate perception of death risk is a prerequisite for advanced cancer patients to make informed end-of-life care decisions. However, there is to date no suitable scale to measure death risk perception. This study was to develop and psychometrically test the death risk perception scale (DRPS) for advanced cancer patients. METHODS: Process of instrument development and psychometric evaluation were used. First, qualitative research, a literature review, brainstorming, a Delphi study, and cognitive interviews were conducted to construct a pretest scale of death risk perception. Second, a scale-based survey was administered to 479 advanced cancer patients. Item, exploratory factor, and confirmatory factor analyses were employed to optimize the scale. The Cronbach's alpha was calculated as a reliability analysis. The validity analysis included construct, convergent, discriminant, and content validity values. RESULTS: A three-dimension, 12-item scale was developed, including deliberative, affective, and experiential risk perception. The confirmatory factor analysis supported the three-factor model with satisfactory convergent and discriminant validity levels. The Cronbach's alpha coefficient for internal consistency was 0.807 and scale-level content validity index was 0.98. CONCLUSIONS: The 12-item DRPS is a reliable and valid instrument for assessing the level of death risk perception in advanced cancer patients. More studies are needed to examine its structure and robustness prior to use.

Malignant tumor increases the risk of all causes in-hospital mortality in critically ill patients with ischemic stroke: analysis of the MIMIC-IV database.

BACKGROUND: Ischemic stroke (IS) and malignant tumor (MT) have high morbidity and mortality rates worldwide, and several associations exist between them. This study aimed to determine the effect of MT on hospital mortality in patients with IS. METHODS: Based on their MT status, participants with IS in the Medical Information Mart for Intensive Care IV (MIMIC-IV) were divided into two groups. The primary outcome was in-hospital all causes mortality. Kaplan-Meier survival analysis was performed to evaluate the intergroup in-hospital mortality, and three Cox regression models were used to determine the association between MT and in-hospital mortality. RESULTS: A total of 1605 participants (749 males and 856 females) were included in the study. The mean age was 72.030 ± 15.463 years. Of these, 257 (16%) patients died in the hospital. Kaplan-Meier analysis showed that the MT group had a significantly lower possibility of in-hospital survival than the non-MT group. In the unadjusted model, in-hospital mortality among MT patients had a higher odds ratio (OR) of 1.905 (95% CI, 1.320-2.748; P < 0.001) than the non-MT group. After adjusting for basic information, vital signs, and laboratory data, MT was also associated with increased in-hospital mortality (OR = 1.844, 95% CI: 1.255-2.708; P = 0.002). CONCLUSIONS: Among the patients with IS, the risk of all causes in-hospital mortality was higher for MT than for patients non-MT. This finding can assist clinicians in more accurately assessing prognosis and making informed treatment decisions.

Association of Life's Essential 8 with all-cause mortality and risk of cancer: a prospective cohort study.

BACKGROUND: No study has concentrated on the association of LE8 with cancer risk and death. We aim to examine the association of LE8 with death and cancer. METHODS: A total of 94733 adults aged 51.42 ± 12.46 years and 77551 participants aged 54.09±12.06 years were enrolled in longitudinal and trajectory analysis respectively. Baseline LE8 was divided into three groups based on the American Heart Association criteria and three trajectory patterns by latent mixture models. We reviewed medical records and clinical examinations to confirm incident cancer during the period from 2006 to 2020. Death information was collected from provincial vital statistics offices. Cox models were used. RESULTS: 12807 all-cause deaths and 5060 cancers were documented during a 14-year follow-up. Relative to participants with high LE8 at baseline, participants with lower levels of LE8 have a significantly increased risk of mortality and incident cancer. All these risks have an increasing trend with LE8 level decreasing. Meanwhile, the trajectory analysis recorded 7483 all-cause deaths and 3037 incident cancers after approximately 10 years. The associations of LE8 with death and cancer were identical to the longitudinal study. In the subtype cancer analysis, LE8 has a strong effect on colorectal cancer risk. Moreover, the cut point is 56.67 in the association between LE8 and death, while the cut point altered to 64.79 in the association between LE8 and incident cancers. These associations were enhanced among younger adults. CONCLUSIONS: There was a significant association of LE8 with death and cancer risk, especially for the young population.