Causal relationships between vitamin E and multiple kidney diseases: evidence from trans-ethnic Mendelian randomization study.

PURPOSE: The association between vitamin E and the risk of kidney disease is well documented in observational studies, but the role of vitamin E in kidney disease remain inconclusive. Here, we evaluated the causal effect of vitamin E on the risk of multiple kidney diseases, including chronic kidney disease, membranous nephropathy, diabetic nephropathy, IgA nephropathy, and dialysis. METHODS: We conducted a two-sample Mendelian randomization analysis from large-scale trans-ancestry genome-wide association studies to determine whether there was a significant causal relationship between vitamin E and multiple kidney diseases in European, American, and Asian ancestry. Instrumental genetic variants associated with vitamin E were selected, and summary statistic-based methods of inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode methods were conducted. Pleiotropy and sensitivity were assessed. RESULTS: We obtained 87 instrumental genetic variants in European ancestry and found no causal relationship between vitamin E and chronic kidney disease, membranous nephropathy, diabetic nephropathy, IgA nephropathy, and dialysis with no heterogeneity and pleiotropy. We obtained 18 instrumental genetic variants in Asian ancestry and vitamin E had no causal relationship with membranous nephropathy, diabetic nephropathy, and IgA nephropathy with no heterogeneity and pleiotropy. In African ancestry, 25 instrumental genetic variants were obtained and no causal relationship was identified with no heterogeneity and pleiotropy. CONCLUSION: Our study first suggested plausible non-causal associations between vitamin E and multiple kidney diseases among different ancestry.

Association between dietary quality and accelerated aging: a cross-sectional study of two cohorts.

Background: Diet quality significantly influences aging processes and age-related health outcomes. This study aims to explore the association between dietary quality and accelerated aging in two large cohorts. Methods: This study collected data from the Kailuan and National Health and Nutrition Examination Survey (NHANES) cohorts; participants' dietary quality was evaluated using the American Heart Association (AHA) dietary score and Healthy Eating Index-2015 (HEI-2015), respectively. Accelerated aging in participants was determined by calculating the difference between phenotypic age and chronological age. Logistic regression models were used to explore the association between dietary quality scores and accelerated aging. Additionally, variations in this association across different subgroups were investigated. To minimize the influence of excessive aging, individuals aged 75 and above were excluded in sensitivity analyses. Results: In this study, we included 33 701 participants (27.3% female, mean age 57.29 ± 11.88) from the Kailuan study and 9285 participants (50.6% female, mean age 49.83 ± 17.62) from NHANES. In the Kailuan cohort, individuals with dietary scores ranging from 3 to 5 exhibited a 22% lower risk of accelerated aging compared to those scoring between 0 and 2 (OR = 0.78, 95% CI = 0.72-0.85). Similarly, in the NHANES cohort, participants in the highest quartile of HEI-2015 experienced a 34% reduction in the risk of accelerated aging compared to those in the lowest quartile (OR = 0.66, 95% CI = 0.52-0.84). Subgroup analyses underscored a more pronounced association between dietary quality and accelerated aging among males and individuals with unhealthy lifestyles. Sensitivity analyses confirmed the robustness of the association between dietary quality and accelerated aging. Conclusion: In summary, our study found a significant association between dietary quality and accelerated aging. Better dietary quality was associated with a reduced risk of accelerated aging, particularly among males, smokers, and participants with unhealthy lifestyles.

Sarcopenic Obesity and Outcomes for Patients With Cancer.

Importance: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) have recently proposed a consensus definition and diagnostic criteria for sarcopenic obesity (SO). Objective: To implement the ESPEN-EASO diagnostic algorithm to investigate the prevalence of SO and its association with outcomes in patients with solid tumor cancers, with particular regard to associations among SO, overall survival (OS), and patient quality of life (QoL). Design, Setting, and Participants: This prospective cohort study included patients diagnosed with solid tumor starting in May 7, 2013, with the last follow-up on June 30, 2022. Patients with solid tumors were categorized into SO and non-SO groups according to ESPEN-EASO criteria. The primary outcome was OS and the secondary outcomes included patient QoL and risk of intensive care unit (ICU) admission. Data were analyzed from June to December 2023. Results: A total of 6790 patients were included in the study (mean [SD] age, 59.64 [10.77] years; 3489 were female [51.4%]). The prevalence of SO was 4.36% (296 of 6790) in the whole cohort and 14.98% (296 of 1976) in the subgroup with obesity. SO prevalence increased with age. During a median (IQR) follow-up period of 6.83 (5.67-7.04) years, 2103 patients died. Cox regression analysis indicated that SO was independently associated with lower OS (hazard ratio [HR], 1.54; 95% CI, 1.23-1.92), which was observed in both men (HR, 1.51; 95% CI, 1.09-2.10) and women (HR, 1.53; 95% CI, 1.12-2.07). SO was also associated with poorer QoL and higher risk of ICU admission (odds ratio, 2.39; 95% CI, 1.06-5.29). Among the diagnostic components of SO, low hand grip strength (HGS) was the only SO component associated with poor OS (HR, 1.15; 95% CI, 1.04-1.28). Conclusions and Relevance: This cohort study of SO found that SO was significantly associated with lower OS, poorer QoL, and higher risk of ICU admission. Weak HGS, 1 of the diagnostic conditions, was the only component of SO associated with OS. The ESPEN-EASO algorithm appears to be an applicable tool to identify cancer-associated SO, which represents a major clinical complication and factor associated with risk for poor outcomes in these patients.

Performance of anthropometry-based and bio-electrical impedance-based muscle-mass indicators in the Global Leadership Initiative on Malnutrition criteria for predicting prognosis in patients with cancer.

BACKGROUND: Reduced muscle mass is a criterion for diagnosing malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria; however, the choice of muscle-mass indicators within the GLIM criteria remains contentious. This study aimed to establish muscle-measurement-based GLIM criteria using data from bio-electrical impedance analysis (BIA) and anthropometric evaluations and evaluate their ability to predict overall survival (OS), short-term outcomes, and healthcare burden in patients with cancer. METHODS: This was a multicenter, prospective study that commenced in 2013 and enrolled participants from various clinical centers across China. We constructed GLIM criteria based on various muscle measurements, including fat-free mass index (FFMI), skeletal muscle index (SMI), calf circumference (CC), midarm circumference (MAC), midarm muscle circumference (MAMC), and midarm muscle area (MAMA). Survival was estimated using the Kaplan-Meier method and survival curves were compared using the log-rank test. Cox proportional hazards regression was used to assess the independent association between the GLIM criteria and OS. The discriminatory performance of different muscle-measurement-based GLIM criteria for mortality was evaluated using Harrell's concordance index (C-index). Logistic regression was used to evaluate the association of the GLIM criteria with short-term outcomes and healthcare burden. RESULTS: A total of 4769 patients were included in the analysis, of whom 1659 (34.8%) died during the study period. The Kaplan-Meier curves demonstrated that all muscle-measurement-based GLIM criteria significantly predicted survival in patients with cancer (all p < 0.001). The survival rate of malnourished patients was approximately 10% lower than that of non-malnourished patients. Cox proportional hazards regression showed that all the muscle-measurement-based GLIM could independently predict the OS of patients (all p < 0.001). The prognostic discrimination was as follows: MAMC (Chi-square: 79.61) > MAMA (Chi-square: 79.10) > MAC (Chi-square: 64.09) > FFMI (Chi-square: 62.33) > CC (Chi-square: 58.62) > ASMI (Chi-square: 57.29). In comparison to the FFMI-based GLIM criteria, the ASMI-based criteria (-0.002, 95% CI: -0.006 to 0.002, p = 0.334) and CC-based criteria (-0.003, 95% CI: -0.007 to 0.002, p = 0.227) did not exhibit a significant advantage. However, the MAC-based criteria (0.001, 95% CI: -0.003 to 0.004, p = 0.776), MAMA-based criteria (0.004, 95% CI: 0.000-0.007, p = 0.035), and MAMC-based criteria (0.005, 95% CI: 0.000-0.007, p = 0.030) outperformed the FFMI-based GLIM criteria. Logistic regression showed that muscle measurement-based GLIM criteria predicted short-term outcomes and length of hospital stay in patients with cancer. CONCLUSION: All muscle measurement-based GLIM criteria can effectively predict OS, short-term outcomes, and healthcare burden in patients with cancer. Anthropometric measurement-based GLIM criteria have potential for clinical application as an alternative to BIA-based measurement.

The effect of hyperlipidemia on overall survival in patients with cancer was differentiated by BMI and hyperlipidemia type.

BACKGROUND AND AIMS: The impact of lipids on the overall survival (OS) of patients with malignancy has not yet been clarified. This study aimed to evaluate the effect of hyperlipidemia on the OS among Chinese patients based on Body Mass Index (BMI) stratifications and hyperlipidemia types. METHOD: The patients in this study were derived from the Investigation of the Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) trial. Kaplan-Meier was used to draw the survival curve, and the log-rank test was used to estimate the survival rates between each group. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: A total of 9054 patients were included in the final study, with a median age of 59 years, and 55.3% (5004) of them were males. Regarding types of hyperlipidemia, only low high-density lipoprotein was an independent risk factor for the prognosis of all patients (HR = 1.35, 95% CI: 1.25-1.45, P < 0.001), while high total cholesterol (HR = 1.01, 95% CI: 0.90-1.15, P = 0.839) and high low-density lipoprotein (HR = 1.03, 95%CI: 0.91-1.16, P = 0.680) were not. In terms of BMI stratification, the effect of triglycerides on prognosis varied; high triglycerides were an independent risk factor for the prognosis of underweight patients (HR = 1.56, 95% CI:1.05-2.32, P = 0.027) and a protective factor for overweight patients (HR = 0.75, 95% CI: 0.63-0.89, P = 0.001). However, for normal-weight patients, there was no significant statistical difference (HR = 0.88, 95%CI: 0.75-1.03, P = 0.108). CONCLUSIONS: The impact of hyperlipidemia on the OS among patients with cancer varied by different BMI and hyperlipidemia types. BMI and hyperlipidemia type ought to be considered in combination to estimate the prognosis of patients with malignancy.

Apolipoprotein A-I levels in the survival of patients with colorectal cancer: a retrospective study.

Background: Abnormal lipid levels have been associated with cancer incidence and progression. However, limited studies have investigated the relationship between apolipoprotein A-I (ApoA-I) and colorectal cancer (CRC). This study assessed the significance of ApoA-I levels in progression-free survival (PFS) and overall survival (OS) of patients with CRC. Methods: Survival curves were compared using Kaplan-Meier analysis, while the predictive values of various lipid indicators in CRC prognosis were evaluated based on receiver operating characteristic curves. The factors influencing PFS and OS in patients with CRC were analyzed using Cox proportional hazards regression models. Finally, the relationship between ApoA-I level and disease recurrence was investigated through logistic regression analysis. The optimal Apo-I level was determined through maximally selected rank statistics. Results: Using the optimal ApoA-I cutoff value (0.9 g/L), the 1,270 patients with CRC were categorized into low (< 0.9 g/L, 275 cases) and high (≥0.9 g/L, 995 cases) ApoA-I groups. Compared with other lipid indicators, ApoA-I demonstrated superior predictive accuracy. The high ApoA-I group exhibited significantly higher survival rates than the low ApoA-I group (PFS, 64.8% vs. 45.2%, P < 0.001; OS, 66.1% vs. 48.6%, P < 0.001). Each one-standard-deviation increase in ApoA-I level was related to a 12.0% decrease in PFS risk (hazard ratio [HR] 0.880; 95% confidence interval [CI], 0.801-0.968; P = 0.009) and an 11.2% decrease in OS risk (HR 0.888; 95%CI, 0.806-0.978; P = 0.015). Logistic regression analysis revealed that patients with low ApoA-I had a 32.5% increased risk of disease recurrence (odds ratio [OR] 0.675; 95%CI, 0.481-0.946; P = 0.0225) compared with those with high ApoA-I. PFS/OS nomograms based on ApoA-I demonstrated excellent prognostic prediction accuracy. Conclusions: Serum ApoA-I level may be a valuable and non-invasive tool for predicting PFS and OS in patients with CRC.

Anthropometrics and cancer prognosis: a multicenter cohort study.

BACKGROUND: Anthropometric indicators have been shown to be associated with the prognosis of patients with cancer. However, any single anthropometric index has limitation in predicting the prognosis. OBJECTIVES: This study aimed to observe the predictive role of 7 anthropometric indicators based on body size on the prognosis of patients with cancer. METHODS: A principal component analysis (PCA) on 7 anthropometric measurements: height, weight, BMI, hand grip strength (HGS), triceps skinfold thickness (TSF), mid-upper arm circumference (MAC), and calf circumference (CAC) was conducted. Principal components (PCs) were derived from this analysis. Cox regression analysis was used to investigate the association between the prognosis of patients with cancer and the PCs. Subgroups and sensitivity analyses were also conducted. RESULTS: Through PCA, 4 distinct PCs were identified, collectively explaining 88.3% of the variance. PC1, primarily characterized by general obesity, exhibited a significant inverse association with risk of cancer-related death (adjusted hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.83, 0.88). PC2 (short stature with high TSF) was not significantly associated with cancer prognosis. PC3 (high BMI coupled with low HGS) demonstrated a significant increase with risk of cancer-related death (adjusted HR: 1.08; 95% CI: 1.05, 1.11). PC4 (tall stature with high TSF) exhibited a significant association with increased cancer risk (adjusted HR: 1.05; 95% CI: 1.02, 1.07). These associations varied across different cancer stages. The stability of the results was confirmed through sensitivity analyses. CONCLUSIONS: Different body sizes are associated with distinct prognostic outcomes in patients with cancer. The impact of BMI on prognosis is influenced by both HGS and subcutaneous fat. This finding may influence the clinical care of cancer and improve the survival of cancer patients.

Obesity-associated metabolic inflammation promotes triple-negative breast cancer progression through the interleukin-6/STAT3/pentraxin 3/matrix metalloproteinase 7 axis.

BACKGROUND: This study aimed to investigate the regulatory mechanism of the adipose factor interleukin (IL)-6 in promoting pentraxin 3 (PTX3) expression in triple-negative breast cancer (TNBC). METHODS: We established an in vitro coculture model of mature adipocytes and TNBC cells using a Transwell system. Cell scratch, Transwell migration, and matrix invasion assays were used to evaluate the migration and invasion abilities of TNBC cells cocultured with adipocytes. Next, we used lentivirus-mediated functional depletion experiments to study PTX3's role in the adipocyte-dependent migration of TNBC cells. RESULTS: After coculturing TNBC cells with adipocytes, PTX3 expression was upregulated, which accompanied enhanced cell migration and invasion. Using GEO data and RNA-seq analysis, we identified PTX3 as a key target gene influenced by the adipose TNBC microenvironment. IL-6 upregulation in the conditioned medium of mature adipocytes and in the serum of high-fat diet mice was associated with this effect, and the recombinant protein IL-6 significantly promoted the migration and invasion of TNBC cells along with the phosphorylation of intracellular STAT3 and the upregulation of PTX3. PTX3 knockdown inhibited TNBC cell migration and eliminated the enhanced migration caused by coculturing with adipocytes. Furthermore, in vivo experiments confirmed that the PTX3 knockdown reduced obesity-induced lung metastasis. Subsequent experiments with cytokines and drug inhibitors confirmed that adipocyte-derived IL-6 promoted PTX3 expression by activating the STAT3 signaling pathway. Additionally, bioinformatic analysis indicated that PTX3 promotes TNBC metastasis by regulating the matrix metalloproteinase (MMP) family. CONCLUSION: Our study elucidated Obesity-related metabolic inflammation promotes the progression via the IL-6/STAT3/PTX3/MMP7 axis.

Phase angle: A robust predictor of malnutrition and poor prognosis in gastrointestinal cancer.

OBJECTIVES: The aim of this study was to investigate the relationship among phase angle (PA), malnutrition, and prognosis in patients with gastrointestinal cancer. METHODS: In total, 870 patients with gastrointestinal cancer were enrolled. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate the association between PA and survival risk. Restricted cubic spline regression was used for flexibility analysis to explore sex-specific associations between PA and survival. Logistic regression was used to assess the relationships among PA, malnutrition, and cachexia. RESULTS: Low PA was closely associated with poor physical conditions, diminished quality of life, and malnutrition. Patients with low PA had a significantly worse prognosis than those with high PA (60.6% versus 72.8%; log-rank P < 0.001). PA was suitable for the prognostic assessment of patients with advanced-stage tumors. Regardless of sex, patients with lower PA showed significantly poorer survival rates. Cox proportional hazards models identified PA as an independent predictor of prognosis in patients with gastrointestinal cancer (hazard ratio (HR)=0.534; 95% confidence interval (CI)=0.409-0.696, P < 0.001). Subgroup analysis indicated that a high PA was an independent risk factor affecting the prognoses of patients with esophageal, liver, and intrahepatic bile duct cancers. Interestingly, variations in PA had a more significant prognostic effect on survival in men than in women. The logistic regression model confirmed that PA is a valuable indicator for assessing malnutrition and cachexia in patients with gastrointestinal cancer. Among all body composition indicators, PA demonstrated the highest accuracy for prognostic prediction. CONCLUSIONS: PA was identified as a robust predictor of malnutrition and poor prognosis in patients with gastrointestinal cancer.

Inflammaging score as a potential prognostic tool for cancer: A population-based cohort study.

This study aimed to develop a clinically applicable inflammaging score by combining the inflammatory status and age of patients. Kaplan-Meier analysis was used to compare survival differences among patients with different grades of inflammation scores. Cox proportional hazard regression analysis was used to explore the relationship between the inflammaging score and survival. As the age of patients increased, their levels of systemic inflammation gradually increased. A unique inverse relationship was found between the level of inflammation and cancer prognosis during the ageing process. Mediation analysis indicated that systemic inflammation mediates 10.1%-17.8% of the association between ageing and poor prognosis. With an increase in the inflammaging score from grades I to V, the survival rate showed a gradient decline. The inflammation score could effectively stratify the prognosis of patients with lung, bronchial, gastrointestinal, and other types of cancers. Compared with grade I, the hazard ratios for grades II-V were 1.239, 1.604, 1.724, and 2.348, respectively. In the external validation cohort, the inflammaging score remained an independent factor affecting the prognosis of patients with cancer. The inflammaging score, which combines ageing and inflammation, is a robust prognostic assessment tool for cancer patients.

Elevated serum homocysteine levels associated with poor recurrence-free and overall survival in patients with colorectal cancer.

This study aimed to evaluate the significance of homocysteine (HCY) levels in predicting recurrence-free survival (RFS) and overall survival (OS) in colorectal cancer (CRC) patients. This retrospective study involved 1272 CRC patients. The risk of mortality increased with increasing HCY levels in CRC patients. The optimal HCY cutoff value in CRC patients was 15.2 µmol/L. The RFS (45.8% vs. 60.5%, p < 0.001) and OS (48.2% vs. 63.2%, p < 0.001) of patients with high HCY levels were significantly lower than those of patients with low HCY levels. Patients with high HCY levels were older, male, had large tumours, high carcinoembryonic antigen (CEA) levels, and long hospital stays, and incurred high hospitalisation costs. Multivariate analysis showed that when HCY levels exceeded 15.2 µmol/L, the risk of adverse RFS and OS increased by 55.7% and 61.4%, respectively. Subgroup analysis showed that HCY levels could supplement CEA levels and pathological staging. We constructed HCY-based prognostic nomograms, which demonstrated feasible discrimination and calibration values better than the traditional tumour, node, metastasis staging system for predicting RFS and OS. Elevated serum HCY levels were strongly associated with poor RFS and OS in CRC patients. HCY-based prognostic models are effective tools for a comprehensive evaluation of prognosis.

Remnant cholesterol is an effective biomarker for predicting survival in patients with breast cancer.

BACKGROUND: Breast cancer is the most common malignancy in women worldwide. The relationship between remnant cholesterol (RC) and the prognosis of patients with breast cancer has not been clearly reported. This study investigated the prognostic value of RC in predicting mortality in patients with breast cancer. METHODS: This study prospectively analysed 709 women patients with breast cancer from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project. Restricted cubic splines were used to analyse the dose-response relationship between RC and breast cancer mortality. The Kaplan-Meier method was used to evaluate the overall survival of patients with breast cancer. A Cox regression analyses was performed to assess the independent association between RC and breast cancer mortality. Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce confounding. Sensitivity analysis was performed after excluding patients with underlying diseases and survival times shorter than one year. RESULTS: A linear dose-response relationship was identified between RC and the risk of all-cause mortality in patients with breast cancer (p = 0.036). Kaplan-Meier survival analysis and log-rank test showed that patients with high RC levels had poorer survival than those with low RC levels (p = 0.007). Univariate and multivariate Cox regression analyses showed that RC was an independent risk factor for mortality in women patients with breast cancer. IPTW-adjusted analyses and sensitivity analyses showed that CR remained a prognostic factor. CONCLUSIONS: RC is an independent risk factor for the prognosis of patients with breast cancer, and patients with higher RC levels have poorer survival.

The relationship between different fatty acids intake and the depressive symptoms: A population-based study.

BACKGROUND: Depression is a common psychological disorder worldwide, affecting mental and physical health. Previous studies have explored the benefits of polyunsaturated fatty acids (PUFAs) intake in depressive symptoms; however, few studies have focused on the association between all types of fatty acids intake and depressive symptoms. Therefore, we explored the relationship between the intake of different fatty acids intake and the risk of depressive symptoms. METHODS: The study was based on the data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES), a large US-based database. We used a nutrient residual model and multi-nutrient density model for the analysis. We calculated the nutrient density and residual in men and women separately, and the fatty acids intake was divided into quartiles based on the sex distribution. The relationship between the depressive symptoms and the intake of different fatty acids was examined using logistic regression; furthermore, we explored the relationships separately in men and women. RESULTS: The intake of monounsaturated fatty acids (MUFAs) and PUFAs, particularly n-3 and n-6 PUFAs, were associated with reduced odds ratios for depressive symptoms. The inverse relationship between the intake of MUFAs, PUFAs, n-3, and n-6 PUFAs and depressive symptoms was stronger in women. The inverse relationship between total fatty acid (TFAs) intake and depressive symptoms existed only in a single model. In contrast, saturated fatty acid (SFAs) intake was not related to depressive symptoms. CONCLUSION: Consuming MUFAs and PUFAs can counteract the depressive symptoms, especially in women.

ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells.

Colorectal cancer (CRC) is a worldwide health concern. Chronic inflammation is a risk factor for CRC, and interleukin-6 (IL-6) plays a pivotal role in this process. Arginine-specific mono-ADP-ribosyltransferase-1 (ART1) positively regulates inflammatory cytokines. ART1 knockdown reduces the level of glycoprotein 130 (gp130), a key transducer in the IL-6 signalling pathway. However, the relationship between ART1 and IL-6 and the resulting effects on IL-6-induced proliferation in CRC cells remain unclear. The aims of this study were to investigate the effects of ART1 knockdown on IL-6-induced cell proliferation in vitro and use an in vivo murine model to observe the growth of transplanted tumours. The results showed that compared with the control, ART1-sh cancer cells induced by IL-6 exhibited reduced viability, a lower rate of colony formation, less DNA synthesis, decreased protein levels of gp130, c-Myc, cyclin D1, Bcl-xL, and a reduced p-STAT3/STAT3 ratio (P < 0.05). Moreover, mice transplanted with ART1-sh CT26 cells that had high levels of IL-6 displayed tumours with smaller volumes (P < 0.05). ART1 and gp130 were colocalized in CT26, LoVo and HCT116 cells, and their expression was positively correlated in human CRC tissues. Overall, ART1 may serve as a promising regulatory factor for IL-6 signalling and a potential therapeutic target for human CRC.

The prognostic value of preoperative D-dimer to albumin ratio for overall survival and progression-free survival in colorectal cancer.

Introduction: This study aimed to explore the predictive value of the D-dimer-to-albumin ratio (DAR) for progression-free survival (PFS) and overall survival (OS) in patients with colorectal cancer (CRC). Methods: The Kaplan-Meier method was used to plot survival curves for PFS and OS. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive efficacy of the DAR for PFS and OS in patients with CRC. Cox proportional hazards regression analysis was used to analyze prognostic factors influencing outcomes. A nomogram based on the DAR was constructed to predict 1-, 3-, and 5-year prognoses of patients with CRC; its predictive ability was evaluated using the concordance index (C-index) and calibration curves. Additionally, the clinical utility of the DAR-based nomogram was validated using an internal randomized validation cohort. Results: A total of 1,339 patients with CRC who underwent surgery were enrolled. The optimal cut-off value for DAR was determined to be 3.320, dividing patients into low (<3.320 [n = 470]) and high (≥3.320 [n = 869]) DAR groups. Compared with other composite immune inflammatory markers, DAR exhibited superior prognostic predictive efficacy. Patients with a high DAR had a significantly worse prognosis than those with a low DAR (PFS, 50.9% versus [vs.] 69.4%, p < 0.001; OS, 52.9% vs. 73.8%, p < 0.001). DAR also demonstrated significant prognostic stratification for most tumor subgroups, particularly in the stage III-IV subgroup and normal carcinoembryonic antigen subgroup. DAR has been identified as an independent predictive indicator of PFS/OS in patients with CRC. For every standard deviation increase in DAR, the risk for PFS/OS in patients with CRC was reduced by 9.5% (hazard ratio [HR] 1.095 [95% confidence interval (CI) 1.013-1.185]; p = 0.022) and 9.3% (HR 1.093 [95% CI 1.012-1.180]; p = 0.024), respectively. The DAR-based nomogram was confirmed to demonstrate good prognostic prediction accuracy and achieved high evaluation in the internal validation cohort. Conclusion: Preoperative DAR is a promising biomarker for predicting PFS and OS among patients with CRC. The DAR-based prognostic prediction nomogram may serve as an effective tool for the comprehensive assessment of prognosis in patients with CRC.

Evaluation and validation of neutrophil to albumin ratio as a promising prognostic marker for all-cause mortality in patients with cancer: a multicenter cohort study.

OBJECTIVES: The practicality and effectiveness of using the prognostic value of the neutrophil-to-albumin ratio (NAR) in evaluating patients with cancer remain unclear, and research is needed to fully understand its potential application in the cancer population. METHODS: The Kaplan-Meier method was used for survival analysis, and the log-rank test was employed for comparison. Univariate and multivariate Cox proportional hazards models were used to determine the prognostic biomarkers, and Logistic regression analysis was conducted to investigate the relationship between NAR and 90-day outcomes and cachexia. RESULTS: The study included 14 682 patients with cancer, divided into discovery (6592 patients), internal validation (2820 patients), and external validation groups (5270 patients). Patients with high NAR had higher all-cause mortality than those with low NAR in the discovery (50.15% versus 69.29%, P < 0.001), internal validation (54.18% versus 70.91%, P < 0.001), and external validation cohorts (40.60% versus 66.68%, P < 0.001). In the discovery cohort, high NAR was observed to be independently associated with all-cause mortality in patients (HR 1.16, 95% CI 1.12-1.19; P < 0.001). Moreover, we validated the promising prognostic value of NAR as a predictor of survival in patients with cancer through internal validation (HR 1.21, 95% CI 1.16-1.27, P < 0.001) and external validation cohorts (HR 1.27, 95% CI 1.21-1.34, P < 0.001). Additionally, in the subgroup analysis by tumor type, high NAR was identified as a risk factor for most cancers, except for breast cancer. CONCLUSIONS: This study showed that NAR is a feasible and promising biomarker for predicting prognosis and cancer cachexia in cancer patients.

Geriatric Nutritional Risk Index Combined with Calf Circumference Can be a Good Predictor of Prognosis in Patients Undergoing Surgery for Gastric or Colorectal Cancer.

OBJECTIVES: To explore the effect of combined hematological and physical measurement indicators on the prognosis of patients undergoing surgery for gastric or colorectal cancer and to screen for the best prognostic indicators. INTRODUCTION: Gastric and colorectal cancer is a widespread health concern worldwide and one of the major contributors to cancer-related death. The hematological and physical measurement indicators have been shown to associate with the prognosis of patients undergoing surgery for gastric or colorectal cancer, respectively, but it is still unclear whether the combination of the two can reflect the prognosis more effectively. METHODS: Thirteen hematological indicators and 5 physical measurement indicators were selected in this study, and the most promising ones were screened using LASSO regression. Then, the best prognostic indicators were selected by time-ROC curves. Survival curves were constructed using the Kaplan-Meier method, and the effects of hematological and physical measurement indicators on the prognosis of patients undergoing surgery for gastric or colorectal cancers were evaluated by Cox proportional risk regression analysis. In addition, the relationship between hematological and physical measurement indicators on secondary outcomes, including length of stay, hospitalization costs, intensive care unit (ICU) admission, and patients' subjective global assessment scores (PGSGA), was explored. RESULTS: After initial screening, among the hematological indicators, the geriatric nutritional risk index (GNRI) showed the highest mean area under the curve (AUC) values. Among body measures, calf circumference (CC) showed the highest mean AUC value. Further analyses showed that the combination of combined nutritional prognostic index (GNRI) and calf circumference (CC) (GNRI-CC) had the best performance in predicting the prognosis of patients undergoing surgery for gastric or colorectal cancers. Low GNRI, low CC, and low GNRI-low CC increased the risk of death by 44%, 48%, and 104%, respectively. Sensitivity analyses showed the same trend. In addition, low GNRI-low CC increased the risk of malnutrition by 17%. CONCLUSION: This study emphasizes that a combination of blood measures and body measures is essential to accurately assess the prognosis of patients undergoing surgery for gastric or colorectal cancers. The GNRI-CC is a good prognostic indicator and can also assess the risk of possible malnutrition.

Temporal relationship between inflammation and metabolic disorders and their impact on cancer risk.

Background: Inflammation and metabolic disorders are closely associated with cancer. Whether inflammation leads to metabolic disorders or vice versa during cancer initiation remains unclear. In this study, we explored this temporal relationship and the co-exposure effect on cancer risk. Methods: This prospective study had two phases. Initially, we examined the temporal relationship between inflammation (high-sensitivity C-reactive protein (CRP)) and metabolic disorders (metabolic syndrome severity Z-score (MetS-Z)) using a 3.98-year survey and cross-lagged analysis. Subsequently, we assessed the connection of co-exposure to inflammation and metabolic disorders, and the risks of overall cancer, as well as specific obesity-related, non-obesity-related, digestive system, lung, and other cancers using an 11.04-year survey and Cox proportional hazard models. Results: The cross-lagged analysis revealed that the path coefficient from baseline CRP to follow-up MetS-Z (ß2 = 0.032; 95% confidence interval (CI) = 0.026, 0.046) was more significant than the path coefficient from baseline MetS-Z to follow-up CRP (ß1 = 0.009; 95% CI = -0.001, 0.019). During the follow-up, 2304 cases of cancer occurred. Compared with the risk of cancer of patients with low average cumulative CRP and MetS-Z, patients with high value had a significantly increased risk (hazard ratio = 1.54, 95% CI = 1.30, 1.83). The mediation analysis showed that MetS-Z mediated the association between CRP levels and overall cancer (12.67%), digestive system cancer (10.16%), and obesity-related cancer risk (13.87%). Conclusions: Inflammation had a greater impact on metabolic disorders than vice versa. Co-exposure to inflammation and metabolic disorders significantly increased the risk of cancer, particularly digestive system and obesity-related cancers. Registration: Chinese Clinical Trial Registry: ChiCTR-TNRC-11001489.

Age Differences in the Association of Sleep Duration Trajectory With Cancer Risk and Cancer-Specific Mortality: Prospective Cohort Study.

BACKGROUND: Baseline sleep duration is associated with cancer risk and cancer-specific mortality; however, the association between longitudinal patterns of sleep duration and these risks remains unknown. OBJECTIVE: This study aimed to elucidate the association between sleep duration trajectory and cancer risk and cancer-specific mortality. METHODS: The participants recruited in this study were from the Kailuan cohort, with all participants aged between 18 and 98 years and without cancer at baseline. The sleep duration of participants was continuously recorded in 2006, 2008, and 2010. Latent mixture modeling was used to identify shared sleep duration trajectories. Furthermore, the Cox proportional risk model was used to examine the association of sleep duration trajectory with cancer risk and cancer-specific mortality. RESULTS: A total of 53,273 participants were included in the present study, of whom 40,909 (76.79%) were men and 12,364 (23.21%) were women. The average age of the participants was 49.03 (SD 11.76) years. During a median follow-up of 10.99 (IQR 10.27-11.15) years, 2705 participants developed cancers. Three sleep duration trajectories were identified: normal-stable (44,844/53,273, 84.18%), median-stable (5877/53,273, 11.03%), and decreasing low-stable (2552/53,273, 4.79%). Compared with the normal-stable group, the decreasing low-stable group had increased cancer risk (hazard ratio [HR] 1.39, 95% CI 1.16-1.65) and cancer-specific mortality (HR 1.54, 95% CI 1.18-2.06). Dividing the participants by an age cutoff of 45 years revealed an increase in cancer risk (HR 1.88, 95% CI 1.30-2.71) and cancer-specific mortality (HR 2.52, 95% CI 1.22-5.19) only in participants younger than 45 years, rather than middle-aged or older participants. Joint analysis revealed that compared with participants who had a stable sleep duration within the normal range and did not snore, those with a shortened sleep duration and snoring had the highest cancer risk (HR 2.62, 95% CI 1.46-4.70). CONCLUSIONS: Sleep duration trajectories and quality are closely associated with cancer risk and cancer-specific mortality. However, these associations differ with age and are more pronounced in individuals aged <45 years. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TNRC-11001489; http://tinyurl.com/2u89hrhx.

Systemic inflammation and insulin resistance-related indicator predicts poor outcome in patients with cancer cachexia.

BACKGROUND: The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. METHODS: In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. RESULTS: The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13-1.33), 34% (internal test cohort, 95%CI = 1.11-1.62), and 35% (external validation cohort, 95%CI = 1.14-1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22-1.71; internal test cohort, HR = 1.62, 95%CI = 1.12-2.36; external validation cohort, HR = 1.61, 95%CI = 1.15-2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05-4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42-3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52-4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24-2.55] in patients with cancer cachexia. CONCLUSION: The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.