The association of serum betaine concentrations with the risk of new-onset cancers: results from two independent nested case-control studies.

Evidence from epidemiologic studies on the association of circulating betaine levels with the incident risk of cancer has been inconsistent. We aimed to investigate the prospective association of serum betaine concentrations with the risk of cancer. We performed two, nested, case-control studies utilizing data from the "H-type Hypertension Prevention and Control Public Service Project" (HHPCP) and the China Stroke Primary Prevention Trial (CSPPT), with 2782 participants (1391 cancer cases and 1391 matched controls) in the discovery cohort, and 228 participants (114 cancer cases and 114 matched controls) in the validation cohort. Odds ratios (OR) of the association between betaine and cancer were calculated using conditional logistic regression models. There was an association between serum betaine as a continuous variable and total cancer (OR = 1.03, 95%CI = 0.99-1.07, p = 0.097). Among cancer subtypes, a positive association was found between serum betaine and the risk of lung cancer, and an inverse association was found with other cancers. Interestingly, a U-shaped association was observed between serum betaine and digestive cancers, with a turning point of 5.01 mmol/L for betaine (betaine < 5.01 mmol/L, OR = 0.82, 95%CI = 0.59-1.14, p = 0.228; betaine ≥ 5.01 mmol/L, OR = 1.08, 95%CI = 1.01-1.17, p = 0.036). In the validation cohort, a significant association between serum betaine as a continuous variable and total cancer (OR = 1.48, 95%CI = 1.06-2.05, P = 0.020) was also found. High serum betaine was associated with increased risk of total cancer and lung cancer, and a U-shaped association was found with the risk of digestive cancers, with a turning point at about 5.01 mmol/L.

Association between insulin resistance related indicators with the prognosis of patients with colorectal cancer.

BACKGROUND: The progression of colorectal cancer (CRC) has been linked to metabolism alteration. Because insulin resistance (IR) is the basic mechanism of metabolism alteration, IR related indicators are considered to be associated with prognostic of CRC. In this study, we compared the prognostic values of common IR related indicators for CRC and selected the best one. Moreover, we explored the association between that indicator and CRC prognosis and possible interactive covariates. METHODS: Medical records of patients with CRC (n = 1765) were retrieved from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. We compared the prognostic values of IR related indicators and select the best one using concordance index (C-index) and area under curve (AUC). Using Cox proportional hazard regression models, we evaluated the association between that indicator and CRC prognosis. Interaction tests were performed to evaluate possible interactions among covariates and the IR related indicator. RESULTS: Results of C-index and AUC indicated that the ratio of low-density lipoprotein-to-high-density lipoprotein (LHR) showed the highest ability to predict the prognosis of patients with CRC. LHR independently predicted CRC prognosis [hazard ratio (HR) = 1.14; 95 % confidence interval (CI) = 1.05-1.22; P = 0.001]. The interactions between LHR, and age (<65 vs. ≥65; P for interaction = 0.001) or neutrocyte-to-lymphocyte ratio (NLR) (<3 vs. ≥3; P for interaction = 0.055) were also observed. CONCLUSION: LHR was found to be the best IR related indicators to predict prognosis of CRC, and it was negatively correlated with the prognosis of patients with CRC. NLR and aging might interact with LHR.

Straw mulch improves soil carbon and nitrogen cycle by mediating microbial community structure and function in the maize field.

This study was conducted to investigate the capability of the microbial community characteristics and soil variables to promote carbon and nitrogen cycles in maize fields under straw mulch. We covered the surface soil of the maize field with different amounts of wheat straw (0 kg/ha, 2,250 kg/ha, and 4,500 kg/ha) and used 16S rRNA and ITS sequencing, Biology ECO-plate, traditional enzymology, TOC analyzer, and HPLC to measure bacterial and fungal community composition and functions, characteristics of microbial carbon source metabolism, carbon and nitrogen fraction, enzyme activity, and organic acid content in the maize rhizosphere and non-rhizosphere. The results indicated that short-term straw mulch insignificantly affected the alpha diversity of bacterial and fungal communities whereas significantly influenced their beta diversity. The results of functional prediction revealed that straw mulch considerably boosted the relative abundances of bacteria belonging to chemoheterotrophy, aerobic chemoheterotrophy, ureolysis, and nitrogen fixation and inhibited fermentation and nitrate reduction in maize rhizosphere soil. These processes primarily drove the C and N cycles in soil. Straw mulch also improved fungal saprotrophs by raising the proportion of Chaetomiaceae and Chaetosphaeriaceae. The Biology ECO-plate results illustrated that straw mulch weakened the metabolism capacity of microbial labile carbon resources. As a result, the labile C and N fractions were raised under straw mulch. Our results also showed that straw mulch primarily regulated the microbial community structure in rhizosphere soil by significantly decreasing Firmicutes and Ascomycota relative abundance while increasing Basidiomycota. The fungal community structure is more than bacterial for affecting soil microbial biomass carbon, readily oxidizable organic carbon, dissolved organic carbon, available nitrogen, ammonium, and nitrate directly and indirectly through malic acid content and cellulase, protease, and amylase activity. Overall, our findings imply that straw mulch might influence the bacterial and fungal community structures, thereby boosting the production of labile C and N components and accelerating the C and N cycle in maize fields.

Effect of γ-PGA and γ-PGA SAP on soil microenvironment and the yield of winter wheat.

Agricultural poly-γ-glutamic acid (γ-PGA) and γ-PGA super absorbent polymer (SAP) are two forms of γ-PGA applied in agriculture. Different quantities of γ-PGA and γ-PGA SAP (40 kg/hm2, 80 kg/hm2, 120 kg/hm2 and 160 kg/hm2) were applied to the soil in order to investigate their effects on the microenvironment of soil root zone and the yield of winter wheat. The soil water content increased with increasing amounts of γ-PGA SAP. The content of nitrate nitrogen and ammonium nitrogen increased with the increasing amounts of γ-PGA, while γ-PGA SAP significantly increased the content of ammonium nitrogen. The number of soil microorganisms and soil enzyme activities in the root zone increased with the addition of γ-PGA and γ-PGA SAP. The yield of winter wheat increased with the addition of γ-PGA or γ-PGA SAP, but the increasing rate decreased when the amount of γ-PGA and γ-PGA SAP exceeded 80 kg/hm2, with increases of 5.95% and 6.77% compared to the control group, respectively. The addition of γ-PGA significantly increased the protein content of wheat grains, and the WUE increased with increasing amounts of γ-PGA and γ-PGA SAP.

Association between C-reactive protein-albumin-lymphocyte (CALLY) index and overall survival in patients with colorectal cancer: From the investigation on nutrition status and clinical outcome of common cancers study.

Background: Colorectal cancer (CRC) is among the most common malignant cancers worldwide, and its development is influenced by inflammation, nutrition, and the immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and evaluated its association with overall survival (OS) in patients with CRC. Methods: The clinicopathological and laboratory characteristics of 1260 patients with CRC were collected from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. Cox regression analysis was performed to assess the association between the CALLY index and OS. A nomogram including sex, age, the CALLY index and TNM stage was constructed. The Concordance Index (C-index) was utilized to evaluate the prognostic value of the CALLY index and classical CRC prognostic factors, such as modified Glasgow prognostic score (mGPS), neutrocyte to lymphocyte ratio (NLR), systemic immune inflammation index (SII), and platelet to lymphocyte ratio (PLR), as well as to assess the prognostic value of the nomogram and TNM stage. Results: Multivariate Cox regression analyses demonstrated that the CALLY index was independently associated with OS in patients with CRC [Hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.87-0.95, P<0.001]. The CALLY index showed the highest prognostic value (C-index = 0.666, 95% CI = 0.638-0.694, P<0.001), followed by mGPS, NLR, SII, and PLR. The nomogram demonstrated higher prognostic value (C-index = 0.784, 95% CI = 0.762-0.807, P<0.001) than the TNM stage. Conclusion: The CALLY index was independently associated with OS in patients with CRC and showed higher prognostic value than classical CRC prognostic factors. The nomogram could provide more accurate prognostic prediction than TNM stage.

AIWW: a new nutrition-screening tool for the oncologic population.

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named age, intake, weight, and walking (AIWW). Malnutrition was defined based on the scored patient-generated subjective global assessment (PG-SGA). Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW, nutritional risk screening 2002 (NRS-2002), and malnutrition screening tool (MST). Clinical benefit was calculated by the decision curve analysis (DCA), integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). A total of 11,360 patients (male, n=6,024 (53.0%) were included in the final study cohort, and 6,363 patients had malnutrition based on PG-SGA. Based on AIWW, NRS-2002, and MST, 7,545, 3,469, and 1,840 patients were at risk of malnutrition, respectively. The sensitivities of AIWW, NRS-2002, and MST risks were 0.910, 0.531, and 0.285, and the specificities were 0.768, 0.946, and 0.975. The Kendall tau coefficients of AIWW, NRS-2002, and MST risks were 0.588, 0.501, and 0.326, respectively. The area under the curve of AIWW, NRS-2002, and MST risks were 0.785, 0.739, and 0.630, respectively. The IDI, cNRI, and DCA showed that AIWW is non-inferior to NRS-2002 (IDI: 0.002 (-0.009, 0.013), cNRI: -0.015 (-0.049, 0.020)). AIWW scores can also predict the survival of patients with cancer. The missed diagnosis rates of AIWW, NRS-2002, and MST were 0.09%, 49.0%, and 73.2%, respectively. AIWW showed a better nutrition-screening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutrition-screening tool for this population.

The prognostic value of the combination of body composition and systemic inflammation in patients with cancer cachexia.

BACKGROUND: Changes in body composition and systemic inflammation are important characteristics of cancer cachexia. This multi-centre retrospective study aimed to explore the prognostic value of the combination of body composition and systemic inflammation in patients with cancer cachexia. METHODS: The modified advanced lung cancer inflammation index (mALI), which combines body composition and systemic inflammation, was defined as appendicular skeletal muscle index (ASMI) × serum albumin/neutrophil-lymphocyte ratio. The ASMI was estimated according to a previously validated anthropometric equation. Restricted cubic splines were used to evaluate the relationship between mALI and all-cause mortality in patients with cancer cachexia. Kaplan-Meier analysis and Cox proportional hazard regression analysis were used to evaluate the prognostic value of mALI in cancer cachexia. A receiver operator characteristic curve was used to compare the effectiveness of mALI and nutritional inflammatory indicators in predicting all-cause mortality in patients with cancer cachexia. RESULTS: A total of 2438 patients with cancer cachexia were enrolled, including 1431 males and 1007 females. The sex-specific optimal cut-off values of mALI for males and females were 7.12 and 6.52, respectively. There was a non-linear relationship between mALI and all-cause mortality in patients with cancer cachexia. Low mALI was significantly associated with poor nutritional status, high tumour burden, and high inflammation. Patients with low mALI had significantly lower overall survival (OS) than those with high mALI (39.5% vs. 65.5%, P < 0.001). In the male population, OS was significantly lower in the low mALI group than in the high group (34.3% vs. 59.2%, P < 0.001). Similar results were also observed in the female population (46.3% vs. 75.0%, P < 0.001). mALI was an independent prognostic factor for patients with cancer cachexia (hazard ratio [HR] = 0.974, 95% confidence interval [CI] = 0.959-0.990, P = 0.001). For every standard deviation [SD] increase in mALI, the risk of poor prognosis for patients with cancer cachexia was reduced by 2.9% (HR = 0.971, 95%CI = 0.943-0.964, P < 0.001) in males and 8.9% (HR = 0.911, 95%CI = 0.893-0.930, P < 0.001) in females. mALI is an effective complement to the traditional Tumour, Lymph Nodes, Metastasis (TNM) staging system for prognosis evaluation and a promising nutritional inflammatory indicator with a better prognostic effect than the most commonly used clinical nutritional inflammatory indicators. CONCLUSIONS: Low mALI is associated with poor survival in both male and female patients with cancer cachexia and is a practical and valuable prognostic assessment tool.

Comprehensive prognostic effects of systemic inflammation and Insulin resistance in women with breast cancer with different BMI: a prospective multicenter cohort.

To investigate the prognostic value of systemic inflammation and insulin resistance in women with breast cancer with different body mass index (BMI). This multicenter, prospective study included 514 women with breast cancer. Multivariate survival analysis showed that patients with high C-reactive protein (CRP), high CRP to albumin ratio (CAR), high lymphocyte to CRP ratio (LCR), high low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LHR), and high triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c) were significantly associated with worse prognosis. The mortality rate of patients with both high CAR and high LHR or both low LCR and high LHR were 3.91-fold or 3.89-fold higher than patients with both low CAR and low LHR or both high LCR and low LHR, respectively. Furthermore, the combination of LCR and LHR significantly predicted survival in patients within the high BMI group. The CRP, CAR, LCR, LHR, and TG/HDL-c were associated with poor survival in women with breast cancer. The combination of CAR and LHR or LCR and LHR could better predict the prognostic outcomes of women with breast cancer, while the combination of LCR and LHR could better predict the prognosis of those patients with overweight or obese patients.

A novel nutrition-related nomogram for the survival prediction of colorectal cancer-results from a multicenter study.

BACKGROUND: Precisely predicting the short- and long-term survival of patients with cancer is important. The tumor-node-metastasis (TNM) stage can accurately predict the long-term, but not short-term, survival of cancer. Nutritional status can affect the individual status and short-term outcomes of patients with cancer. Our hypothesis was that incorporating TNM stage and nutrition-related factors into one nomogram improves the survival prediction for patients with colorectal cancer (CRC). METHOD: This multicenter prospective primary cohort included 1373 patients with CRC, and the internal validation cohort enrolled 409 patients with CRC. Least absolute shrinkage and selection operator regression analyses were used to select prognostic indicators and develop a nomogram. The concordance (C)-index, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the prognostic discriminative ability of the nomogram, TNM stage, Patient-Generated Subjective Global Assessment (PGSGA), and TNM stage + PGSGA models. The overall survival (OS) curve of risk group stratification was calculated based on the nomogram risk score. RESULTS: TNM stage, radical resection, reduced food intake, activities and function declined, and albumin were selected to develop the nomogram. The C-index and calibration plots of the nomogram showed good discrimination and consistency for CRC. Additionally, the ROC curves and DCA of the nomogram showed better survival prediction abilities in CRC than the other models. The stratification curves of the different risk groups of the different TNM categories were significantly different. CONCLUSION: The novel nomogram showed good short- and long-term outcomes of OS in patients with CRC. This model provides a personalized and convenient prognostic prediction tool for clinical applications.

Systemic inflammation with sarcopenia predicts survival in patients with gastric cancer.

OBJECTIVE: The levels of platelet-related inflammation indicators and sarcopenia have been reported to affect the survival of patients with cancer. To evaluate the prognostic influence of platelet count (PLT), platelet lymphocyte ratio (PLR), and systemic immune inflammation index (SII), and SII combined with sarcopenia on the survival of patients with gastric cancer (GC). METHODS: A total of 1133 patients with GC (812 male and 321 female, average age: 59.43 years) were evaluated. Receiver-operating characteristic curves were used to determine the best cutoff values of PLT, PLR, and SII, and univariate and multivariate Cox risk regression models were used to evaluate whether SII is an independent predictor of overall survival (OS). The prognostic SS (SII-sarcopenia) was established based on SII and sarcopenia. Finally, a comprehensive analysis of the prognostic SS was performed. RESULTS: SII had the strongest prognostic effect. The SII and OS of patients with GC were in an inverted U-shape (adjusted HR = 1.07; 95% CI 0.97-1.19; adjusted P = 0.179). In patients with SII > 1800, SII was negatively correlated with OS (adjusted HR = 0.57; 95% CI 0.29-1.12; adjusted P = 0.102), however, there is no statistical difference. Interestingly, a high SS was associated with a poorer prognosis. The higher the SS score was, the worse the OS (P < 0.001). CONCLUSION: SII is an independent prognostic indicator of GC, and high SII is related to poor prognosis. A higher SS score had worse survival. Thus, the prognostic SS is a reliable predictor of OS in patients with GC.

Nutrition-inflammation marker enhances prognostic value to ECOG performance status in overweight or obese patients with cancer.

BACKGROUND: Overweight or obese cancer patients are more likely to develop a proinflammatory status. The aim of this study was to investigate whether the nutrition-inflammation marker can provide additional prognostic information on top of well-established Eastern Cooperative Oncology Group performance status (ECOG-PS) in overweight or obese patients with cancer. METHODS: A total of 1667 overweight or obese cancer patients were enrolled in this study. We assessed the prediction accuracy of 10 nutrition-inflammation markers by time-dependent receiver operating characteristic (ROC) and elucidated their association with overall survival by the Kaplan-Meier method and a Cox model. RESULTS: In this analysis, the majority of patients had a good performance status (ECOG-PS score ≤1; 88.3%). Both the area under ROC curves and the C-index of the lymphocyte-C-reactive protein ratio (LCR) demonstrated that LCR was the most significant nutrition-inflammation marker correlated with survival. In patients with good ECOG-PS, a low LCR was significantly associated with poorer prognosisand enhanced the predictive ability of one-year mortality. For specific tumor types, a low LCR was an independent prognostic factor for lung cancer, upper gastrointestinal cancer, and colorectal cancer, and it tended to be a significant predictor for breast cancer. In addition, those patients with a combined low LCR and poorer ECOG-PS (ECOG-PS score >1) showed the worst prognosis. CONCLUSION: The LCR is more strongly associated with overall survival than other nutrition-inflammation markers, and it is able to further detect patients with worse prognosis on top of ECOG-PS in overweight or obese patients with cancer.

Hand grip strength-based cachexia index as a predictor of cancer cachexia and prognosis in patients with cancer.

BACKGROUND: The cachexia index is a useful predictor for cancer cachexia and prognostic assessment. However, its use is limited because of high testing costs and complicated testing procedures. Thus, in this study, we aimed to develop a hand grip strength (HGS)-based cancer cachexia index (H-CXI) as a potential predictor of cancer cachexia and prognosis in patients with cancer. METHODS: Here, 14 682 patients with cancer were studied, including the discovery (6592), internal validation (2820) and external validation (5270) cohorts. The H-CXI was calculated as [HGS (kg)/height (m)2  × serum albumin (g/L)]/neutrophil-to-lymphocyte ratio. The Kaplan-Meier method was used to create survival curves, and the log-rank test was used to compare time-event relationships between groups. A Cox proportional hazard regression model was used to determine independent risk factors for overall survival (OS). Logistic regression analysis was used to assess the association of the H-CXI with short-term outcomes and cancer cachexia. RESULTS: There was a significant non-linear relationship between the H-CXI and OS in all cohorts. Patients with a low H-CXI had significantly lower OS than those with a high H-CXI in the discovery cohort (6-year survival percentage: 55.72% vs. 76.70%, log-rank P < 0.001), internal validation cohort (6-year survival percentage: 55.81% vs. 76.70%, log-rank P < 0.001), external validation cohort (6-year survival percentage: 56.05% vs. 75.48%, log-rank P < 0.001) and total cohort (6-year survival percentage: 55.86% vs. 76.27%, log-rank P < 0.001). Notably, the prognostic stratification effect of the H-CXI in patients with advanced-stage disease was more significant than that in patients with early-stage disease. The multivariate Cox proportional risk regression model confirmed that a low H-CXI negatively affected the prognosis of patients with cancer in the discovery cohort [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.71-0.80, P < 0.001], internal validation cohort (HR 0.79, 95 %CI 0.72-0.86, P < 0.001), external validation cohort (HR 0.84, 95% CI 0.79-0.89, P < 0.001) and total cohort (HR 0.80, 95% CI 0.77-0.83, P < 0.001). Multivariate logistic regression models showed that a low H-CXI was an independent risk factor predicting adverse short-term outcomes and cancer cachexia in patients with cancer. CONCLUSIONS: The simple and practical H-CXI is a promising predictor for cancer cachexia and prognosis in patients with cancer.

Glucose to lymphocyte ratio predicts prognoses in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is characterized by high morbidity and mortality. Inflammatory, metabolic, and immune factors are closely related to survival of patients with CRC, but their combined impact is unknown. Hence, we chose and evaluated the prognostic value of glucose to lymphocyte ratio (GLR) and a nomogram that include GLR for patients with CRC. METHODS: A total of 1448 patients with CRC were included in our study, and their baseline clinicopathological characteristics and laboratory investigations were collected for analysis. We used Cox proportional hazard regression analyses (both univariate and multivariate) to determine prognostic values of clinical indicators. A nomogram was constructed, and concordance index (C-index) was used to assess the predictive power. RESULTS: Multivariate analyses demonstrated GLR as an independent prognostic factor (hazard ratios 1.060; 95% confidence interval 1.030-1.091; p < .001). A nomogram was constructed integrating factors with clinical significance (sex) and those with independent prognostic value (age, body mass index, tumor stage, and GLR), and the model showed a C-index of .778 (.757-.799), which was higher than that of .738 (.717-.759) for tumor stage. CONCLUSION: GLR can independently predict the prognoses of patients with CRC, and our nomogram provides more accurate prediction than TNM staging.

Handgrip weakness, systemic inflammation indicators, and overall survival in lung cancer patients with well performance status: A large multicenter observational study.

BACKGROUND: Systemic inflammation and handgrip weakness have been used to predict mortality in many cancers. The purpose of current study was to evaluate the association of co-occurrence of inflammation indicators and handgrip weakness with overall survival (OS) of lung cancer (LC) patients with good performance status. METHODS: The cutoff points for handgrip strength (HGS) and the four inflammation indicators were calculated using Maxstat. The time-dependent receiver operating characteristic curve and C-index were used to select optimal inflammation indicator for predicting OS of LC patients. The Cox proportional hazard regression model was used to calculate the hazard ratio (HR) of mortality. Kaplan-Meier curves were constructed to evaluate the association of indicators and the OS of LC patients. RESULTS: Among the 1951 patients, the mean ± standard deviation (SD) age was 60.6 ± 9.9 years, and 1300 (66.6%) patients were male. In patients with good performance status (PS), handgrip weakness (HR, 1.49; 95% confidence interval [95% CI], 1.30-1.70, p < 0.001) and low advanced lung cancer inflammation index (ALI) (HR, 2.05; 95%CI, 1.79-2.34, p < 0.001), high systemic immune-inflammation index (SII) (HR, 1.91; 95%CI, 1.66-2.19, p < 0.001), high platelet: lymphocyte ratio (PLR) (HR, 1.60; 95%CI, 1.40-1.82, p < 0.001), or high neutrophil: lymphocyte ratio (NLR) (HR, 2.01; 95%CI, 1.76-2.30, p < 0.001) were associated with increased mortality risk of LC patients. ALI had better C-index (0.624) and time-AUC in the prediction of OS in LC patients with good PS than other three combinations. The co-occurrence of handgrip weakness and low ALI more than doubled the risk of death in LC with good PS (HR, 2.44; 95% CI, 2.06-2.89, p < 0.001). CONCLUSION: In LC patients who have good PS, patients with combined handgrip weakness and low ALI have the worst prognosis. THE TRIAL REGISTRATION NUMBER: ChiCTR1800020329.

Prognostic value of the modified advanced lung cancer inflammation index in overweight or obese patients with lung cancer: Results from a multicenter study.

BACKGROUND: This study aimed to explore the relationship between the modified advanced lung cancer inflammation index (mALI) and the survival of overweight or obese patients with lung cancer (LC). METHODS: The mALI was defined as the appendix skeletal muscle index multiplied by the serum albumin level/neutrophil-to-lymphocyte ratio. The cutoff values for males and females were assessed separately. Survival curves were estimated using the Kaplan-Meier method, and statistical differences were determined using the log-rank test. Univariate and multivariate Cox proportional hazards models were used for the survival analysis. The area under the receiver operating characteristic curve was used to compare the prognostic value of mALI with other nutrition assessment indicators. RESULTS: The mALI cut-offs for males and females were 8.59 and 8.26, respectively. Malnutrition, high systemic inflammation, and advanced stage for overweight or obese LC patients were found to be correlated with a low mALI. The median survival of patients with a low mALI was significantly lower than patients with a high mALI by approximately 25 months. In addition, the mALI can be used as an effective supplement to the traditional pathological stage. Multivariable analysis found that mALI was an independent prognostic factor of overall survival (hazard ratio = 0.531; 95% CI, 0.402-0.700; P < 0.001). The prognostic predictive performance of mALI was superior to that of other nutrition assessment indicators. CONCLUSIONS: The mALI was an independent risk factor for the prognosis of overweight or obese LC patients, and a useful supplement to the pathological stage.

Efficacy of Global Leadership Initiative on Malnutrition as potential cachexia screening tool for patients with solid cancer.

PURPOSE: Cachexia has a very high prevalence in patients with cancer, and lacks effective screening tools yet. Global Leadership Initiative on Malnutrition (GLIM) is a novel malnutrition assessment tool, with increased important roles in malnutrition diagnosis for patients with cancer. However, whether GLIM can be used as an effective screening tool remains unknown. METHODS: We performed a multicenter cohort study including 8,478 solid tumor patients from 40 clinical centers throughout China. Cachexia was diagnosed based on the 2011 international cancer cachexia consensus. The receiver operating characteristic curves (ROC) and decision curve analysis (DCA) were developed to determine the efficacy and clinical net benefit of GLIM and Patient-Generated Subjective Global Assessment (PG-SGA) in the detection of cancer cachexia, respectively. RESULTS: According to the consensus guidelines, 1,441 (17.0%) cancer patients were diagnosed with cachexia among 8,478 patients in the present study. The sensitivity of one-step GLIM and two-step GLIM for detecting cachexia were 100 and 88.8%, respectively, while that of PG-SGA was 86.2%. The accuracies of one-step GLIM and two-step GLIM reached 67.4 and 91.3%, which were higher than that of PG-SGA (63.1%). The area under the curves (AUCs) of one-step GLIM (0.835) and two-step GLIM (0.910) were higher than PG-SGA (0.778) in patients with cancer. The DCA also revealed that two-step GLIM had better clinical effect than PG-SGA between 20-50% threshold probabilities. CONCLUSION: GLIM could be used as an effective tool in screening cancer cachexia, two-step GLIM criteria show more accurate while one-step GLIM criteria is more sensitive. TRIAL REGISTRATION: ChiCTR1800020329.

A novel inflammation-nutrition biomarker score for predicting prognosis of patients with cancer: results from a multicenter study.

BACKGROUND: This study aimed to develop an innovative inflammation-nutrition biomarker score (INS) system to stratify the prognoses of patients with cancer. METHODS: A total of 5,221 patients with cancer from multiple centers in China between June 2010 and December 2017 were enrolled in this prospective cohort study. We compared the commonly used inflammation and nutrition biomarkers and selected the most valuable to develop the novel INS system. Survival curves were assessed using the Kaplan-Meier method and the log-rank test to evaluate the difference in survival rates between groups. The Cox proportional hazards model was used to investigate the association between biomarkers and all-cause mortality. RESULTS: As the risk stratification of INS increased (1 to 5), the rate of death for cancer patients gradually increased (25.43% vs. 37.09% vs. 44.59% vs. 56.21% vs. 61.65%, p < 0.001). The INS system was associated with all-cause mortality in patients with cancer. Patients with both high inflammation and nutrition risk (INS = 5) were estimated to have much worse prognosis than those with neither (HR, 2.606; 95%CI, 2.261-3.003, p < 0.001). Subsequently, the results of randomized internal validation also confirmed that INS system had an ideal effect in identifying adverse outcomes. In addition, the INS system could be used as a supplement to pathological stages in prognosis assessment, and had a higher predictive value in comparison with the constitute biomarkers. Patients with a high INS had less functional ability, reduced quality of life, and were at high risk of malnutrition, cachexia, and poor short-term outcomes. CONCLUSION: The INS system based on inflammation and nutrition biomarkers is a simple and effective prognostic stratification tool for patients with cancer, which can provide a valuable reference for clinical prognosis assessment and treatment strategy formulation.

Sex differences in the association of triceps skinfold thickness and colorectal cancer mortality.

OBJECTIVES: Triceps skinfold thickness (TSF) is an economical and effective anthropometric method for estimating cellulite. It has attracted increasing attention as a parameter to assess cancer prognosis. Owing to physiologic differences, the sex-specific value of TSF in the prognostic assessment of colorectal cancer (CRC) is unclear. The aim of this study was to explore the sex differences in the association of TSF and CRC mortality and provide practical clinical guidelines for optimizing prognostic strategies and nutritional guidance for patients with CRC. METHODS: Restricted cubic spline (RCS) regression was used to flexibly analyze the sex-specific relationship between continuous TSF and mortality. Cox regression analysis was used to estimate the independent association between TSF and mortality in CRC patients. Finally, the study population was randomly allocated to two validation cohorts for internal randomization validation. RESULTS: We found an L-shaped association between the TSF and survival of CRC patients. Multivariable-adjusted RCS showed that TSF was associated with non-significant reduced mortality in men (P = 0.076). However, in women, continuous TSF was significantly associated with reduced mortality (P = 0.002). Multivariable-adjusted Cox regression analyses confirmed that TSF was an independent factor affecting the prognosis of women with CRC (hazard ratio [HR], 0.834; 95% confidence interval [CI], 0.748-0.930; log-rank P = 0.001), but not men with CRC (HR, 0.943; 95% CI, 0.869-1.024; log-rank P = 0.161). TSF was also an independent factor for predicting life function, cachexia, and malnutrition in patients with CRC. The randomization internal validation also showed a stronger association between TSF and all-cause mortality in women than in men. CONCLUSIONS: TSF is an independent factor affecting the prognosis of women with CRC; however, the prognostic value of TSF in men with CRC may be limited.

Association of systemic inflammation and low performance status with reduced survival outcome in older adults with cancer.

BACKGROUND: Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS). METHODS: We included 1767 older adults with cancer (66.2% males, 70.97 ± 5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses. RESULTS: The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p < 0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p < 0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months). CONCLUSION: LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

Novel Diagnostic and Prognostic Tools for Lung Cancer Cachexia: Based on Nutritional and Inflammatory Status.

Background: Cachexia is one of the most common complications affecting lung cancer patients that seriously affects their quality-of-life and survival time. This study aimed to analyze the predictors and prognostic factors of lung cancer cachexia as well as to develop a convenient and accurate clinical prediction tool for oncologists. Methods: In this multicenter cohort study, 4022 patients with lung cancer were retrospectively analyzed. The patients were randomly categorized into training and verification sets (7:3 ratio). Univariate and multivariate logistic regression analyses were performed to determine the risk factors of cachexia in patients with lung cancer. Cox regression analysis was applied to determine independent prognostic factors in the patients with lung cancer cachexia. Meanwhile, two nomograms were established and evaluated by time-dependent receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). Results: Stage, serum albumin, ALI, anemia, and surgery were independent risk factors for cachexia in patients with lung cancer. Patients with lung cancer cachexia have a shorter survival time. Sex, stage, serum albumin, ALI, KPS score, and surgery served as independent prognostic factors for patients with lung cancer cachexia. The area under the curves (AUCs) of diagnostic nomogram in the training and validation sets were 0.702 and 0.688, respectively, the AUCs of prognostic nomogram in the training set for 1-, 3-, and 5-year were 0.70, 0.72, and 0.75, respectively, while in the validation set the AUCs were 0.71, 0.75, and 0.79, respectively. The calibration curves and DCA of the two nomograms were consistent and the clinical benefit rate was high. Conclusion: Cachexia brings an additional economic burden and worsens the prognosis of lung cancer patients. The two nomograms can accurately screen and predict the probability of occurrence of cachexia in lung cancer and the prognosis of patients with lung cancer cachexia, and guide clinical work.