Value of combining the serum D-lactate, diamine oxidase, and endotoxin levels to predict gut-derived infections in cancer patients

Objective:This is a retrospective observational cohort study.The objective of this retrospective observational cohort study was to evaluate the value of the combined serum D-lactic acid,diamine oxidase(DAO),and endotoxin levels to predict intestinal barrier impairment and gut-derived infection(GDI)in cancer patients.Methods:Cancer patients receiving chemotherapy or palliative care treatment at our hospital were enrolled in the study.The serum concentrations of DAO,D-lactic acid,and endotoxin were determined using the intestinal barrier function biochemical index analysis system.The patients'infection information came from the hospital's Medicom Prescription Automatic Screening System and themedical records.Three hundred fifty-three cancer patients were included in the study(53.8%female,73.7%cancer stage IV,27.8%had bowel obstruction).Results:The total incidence of GDI was 33.4%(118/353).The median length of hospital stay was 16 days for patients with GDI,compared with 7 days for patients without GDI(P<0.001).The media hospitalization costs were¥27,362.35 for patients with GDI compared with¥11,614.08 for patients without GDI(P<0.001).The serum concentrations of DAO,D-lactic acid,and endotoxin were significantly higher in patients with GDI.As malignant bowel obstruction(MBO)worsened,the concentrations of DAO,D-lactic acid,and endotoxin increased.Multivariate logistic regression models revealed that the DAO,endotoxin,IL-6,and C-reactive protein levels were significantly associated with an increased risk of GDI.In addition,we also found a fivefold increased risk of infection in patients withMBO compared with those without bowel obstruction(OR=6.210,P<0.001).All of the areas under the receiver operating characteristic curve(AUCs)for DAO,D-lactate,and endotoxin to predict GDI were<0.7(AUC=0.648,P<0.001;AUC=0.624,P<0.01;AUC=0.620,P<0.01,respectively).However,when the parameters were combined(DAO+D-lactate+endotoxin),the predictive power increased significantly(AUC=0.797,P<0.001).Moreover,combining these intestinal barrier indicators and the presence of MBO had better power to predict GDI than either alone(AUC=0.837,P<0.001).Conclusions:Combining the serum DAO,D-lactic acid,and endotoxin levels was a better predictor of GDI than any of the indicators alone,and combining these with the diagnosis of MBO could further improve the efficacy for predicting GDI.

Malnutrition and Quality of Life in Chinese Cancer Patients: a Clinical Study of 23,994 Subjects

Background Malnutrition is common in patients with cancer,and can negatively impact their quality of life(QoL)and even survival.However,there is currently no large data available on the prevalence of malnutrition in Chinese cancer patients.This study evaluated the prevalence of malnutrition and the QoL of Chinese patients with locoregional,recurrent or metastatic cancer.Methods We conducted a nationwide observational,multi-center,hospital-based cross-sectional study within the Chinese Society of Nutritional Oncology(CSNO)Network.All of the patients were diagnosed with one of the following 18 different types of malignant tumors:lung cancer,gastric cancer,liver cancer,colorectal cancer,breast cancer,esophageal cancer,cervical cancer,endometrial cancer,nasopharyngeal carcinoma,malignant lymphoma,leukemia,pancreatic cancer,ovarian cancer,prostate cancer,bladder cancer,brain cancer,biliary tract malignant tumors or gastrointestinal stromal tumors.These patients were enrolled from 72 hospitals located in different regions of China.The patients’nutritional status was evaluated based on the body mass index(BMI),loss of bodyweight,laboratory measurements and patient generated-subjective global assessment(PG-SGA)scores.The cancer patients’physical status and QoL were assessed by the Karnofsky Performance Status(KPS)questionnaire and the European Organization for Research and Treatment of Cancer(EORTC)QLQ-C30 questionnaire,respectively.Results From December 2013 to April 2016,23,994 patients hospitalized for cancer treatment(such as surgery,chemotherapy or radiotherapy)were enrolled in the study.The patients included 12,494(52.9%)males and 11,124(47.1%)females.The mean age was 55.8±13.7 years.The proportions of patients in cancer stagesⅠ,Ⅱ,Ⅲ,Ⅳand uncertain were 11.5%,20.3%,27.5%,30.2%and 10.5%,respectively.Among the 23,994 inpatients,the proportions of patients who were underweight(BMI<18.5 kg/m2),normal(18.5 kg/m2<BMI<24 kg/m2),overweight(24 kg/m2≤BMI<28 kg/m2)and obese(BMI≥28 kg/m2)were 9.3%,59.9%,26.1%and 4.7%,respectively.A total of 18.3%(4,101/22,424)of patients had lost 5%or more of their bodyweight within the past month and 19.6%(2,463/12,538)of patients had lost 10%or more of their bodyweight within the past 6 months.According to the PG-SGA scores,26.6%of the patients were severely malnourished(score≥9),31.3%were moderately malnourished(scores 4~8).A total of 22.2%of patients had a serum albumin level lower than 35g/L.Only 8.6%(2056/23,991)of the patients had severe KPS scores(≤60).The patients with these severe KPS scores were most frequently among those with cancers of the brain(19.7%),prostate(18.0%),pancreas(15.5%)and bladder(15.0%).Based on the QLQ-C30 score,11.6%of patients had a poor QoL.The PG-SGA score and global QoL were correlated(r=-0.593,P<0.001).Conclusion The prevalence of malnutrition in patients with cancer is relatively high,and is related to a poorer QoL.The present findings should be kept in mind when assessing cancer patients,because addressing the patient’s problems in nutritional status would be expected to improve both the clinical outcomes and QoL in cancer patients with malnutrition.

Extension Protocol for the Investigation on Nutrition Status and Clinical Outcome of Patients with Common Cancers in China(INSCOC)Study:2021 update

Background Malnutrition is common in patients with cancer,and this adversely affects the survival and quality of life of patients.Chinese Society for Nutritional Oncology issued a multi-center,large-scale,long-term follow-up prospective study,the Investigation on Nutrition Status and Clinical Outcome of Patients with Common Cancers in China(INSCOC study)since 2013.This is an extension to the previous 2013-2020 study protocol.This study still sought to:①address the prognostic impact of nutritional factors and quality of life on cancer patient survival;②describe the overall and cancer-specific incidence and/or distribution of malnutrition and different measurements of patient quality of life.Methods and study design This is an observational,multi-centered,hospital-based prospective cohort study.Data collection will be performed at baseline(within 48 hours after patient admission),during the hospital stay and 30 days after hospital admission.Follow-up will be conducted for 1-20 years after enrollment.The primary outcome will be the all-cause mortality/overall survival,and secondary outcomes will be the length of hospital stay and costs of hospitalization.Study factors will include demographic characteristics,tumor characteristics,information about chronic diseases,hematological measurements(e.g.,red blood cell count,total lymphocyte counts,hemoglobin,albumin,prealbumin,creatinine,C-reactive protein,IL-6),anthropometric measurements(e.g.,height,weight,arm circumference,arm muscle circumference,triceps skinfold thickness,and waist circumference),body composition parameters,PG-SGA scores,quality of life(as indicated by the QLQ-C30 questionnaire),muscle mass(as indicated by the calf circumference),muscle strength(as indicated by the handgrip strength),muscle function(as indicated by the six-meter walking speed test)and physical status assessments(as indicated by the Karnofsky Performance Status scores).This clinical study protocol was approved by local Ethics Committees of all the participating hospitals.Written informed consent is required for each subject included.Discussion This multi-center,large-scale,long-term follow up prospective study will help improve the diagnosis of malnutrition in cancer patients and identify the risk factors associated with adverse clinical outcomes.The anticipated results of this study will highlight the need for a truly scientific appraisal of nutrition therapy in Chinese oncology populations,and finally help treat the potentially reversible elements of malnutrition in cancer patients to improve their clinical outcomes in the future.

Fitness Age Score and the Risk of Long-Term Care Insurance Certification—The Kyoto-Kameoka Longitudinal Study

Long-Term Care Insurance System has been introduced to provide appropriate care for the elderly who needs nursing care in Japan. Physical function is one of most important function for the elderly to live independently. A previous study had established a Fitness Age Score (FAS) based on a theory for biomarker of aging. This study clarified whether the FAS could be used to predict the need for certification of long-term care (CLTC) in independent elderly people. We included 939 independent, community-dwelling-elderly (average age, 74.4 years) whose physical function was measured and for whom the CLTC was tracked for 24 months. The FAS comprised five physical fitness items: Walking time, grip strength, one-leg standing, vertical jump, and functional reach test. Based on the FAS, we calculated the odds ratio (OR) for the CLTC. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) was used for further analysis. We also used the Youden Index (YI), minimum distance method (MD), and two-graph ROC method (TG) to calculate cutoff values (CVs) for screening. We divided subjects into the low and high physical fitness group with CVs. We developed cumulative CLTC curves using the Kaplan-Meier method. Sixteen people could not be tracked for the full 24 months. The measurement of FAS was completed for 798 people, of whom 28 became CLTC. The measurement of FAS was not completed for 125 people, of whom 21 became CLTC. The CLTC OR for people with incomplete FAS was 5.553. The AUC was 0.72 (p < 0.001). The CVs for the FAS were -0.29 for YI (sensitivity, 92.9% and specificity, 40.4%), -1.23 for MD (57.1% and 73.4%), and -0.81 for TG (60.7% and 60.9%). The cumulative CLTC curves according to CVs all showed significant differences (p = 0.000 - 0.020). In conclusion, the FAS can be used to predict CLTC.

High Risk of Malnutrition in Uyghur Patients with Cancer in China

Background Patients with advanced cancer often present with malnutrition.Globally,minority populations frequently suffer from higher rates of malnutrition than the majority group.It was unknown whether the nutritional status of cancer patients is different between ethicality groups(i.e.Uyghur and Han)in China.Methods A total of 251 Uyghur cancer patients were enrolled from the Xinjiang Kashgar First People's Hospital in the INSCOC Program.The Han patients were 1∶1 matched to Uyghur patients by age,gender and type of cancer from 72 hospitals around China in INSCOC Program.The nutritional risk and nutritional status were assessed using the Nutrition Risk Screening 2002(NRS 2002)and Patient-Generated Subjective Global Assessment(PG-SGA),respectively.Then,the functional status of cancer patients was determined based on the Karnofsky Performance Status(KPS).Results The incidence of an abnormal NRS-2002(≥3),PG-SGA(≥4),and KPS(≤70)was significantly different(86.1%vs 59.0%,70.5%vs 27.5%,and 18.7%vs 4.0%,respectively P<0.05).The abnormal rate of laboratory indicators in Uyghur cancer patients was significantly higher than that in Han cancer patients,including total protein,albumin,serum total bilirubin,direct bilirubin,HDL-C,white blood cell,lymphocyte,red blood cell,and platelet(all P<0.05).The abnormal rates of TSF,HGS and CC were significantly higher than that of Han nationality patients(17.5%vs 9.7%,39.6%vs 19.6%,29.1%vs 15.2%,P<0.001).The nutritional support rate of Uyghur patients was lower than that of Han patients(0%vs 16.3%).After adjusting for potential risk factors,malnutrition was associated with gender(female,OR=0.35,95%CI=0.13-0.92,P=0.034),age(>60 years,OR=5.32,95%CI=1.46-19.41,P=0.011),cancer type(gastroesophageal tumor,OR=33.62,95%CI=3.42-330.67,P=0.003),and treatment methods(received radical tumor resection,OR=5.78,95%CI=1.45-23.08,P=0.008;received radiotherapy or chemotherapy:OR=7.69,95%CI=2.27-26.04,P<0.001).Conclusions The nutritional status of Uyghur cancer patients is worse than that of Han patients and the Uyghur patients with poor nutritional status lack the necessary nutritional support.

Nutritional Assessment of Gynecological Cancer Patients in China

Background Malnutrition is common among cancer patients,but few studies have evaluated the nutritional status among gynecological cancer patients in China.This study aimed to assess the nutritional status of women with gynecological cancer using the patient-generated subjective global assessment(PG-SGA).Methods Data for gynecological cancer patients treated at 44 tertiary hospitals were retrieved from a multicenter study on tumor nutrition.The R Software was used for statistical analyses.Univariate analyses of PG-SGA scores were performed using the Chi-squared test for categorical variables and the Wilcoxon-rank sum test or Kruskal-Wallis test for continuous variables,as appropriate.The significance level was 0.05.Results Data for 1962 women with three types of gynecological cancer(cervical,uterine and ovarian cancer)were used for the data analysis.The median PG-SGA score was 4(interquartile range,IQR:1,8),the median participants’age was 51(IQR:46,59)years old,and the patients had a median BMI of 22.9(IQR:20.7,25.4).The percentages of women who had a medical co-morbidity,or had undergone any radical resection,chemotherapy,or radiotherapy were approximately 27.7%,55.4%,52.5%,and 30.2%,respectively.The levels of serum albumin and high density lipoprotein cholesterol(HDL-C)were 40.1g/L(IQR:36.8,43.1)and 1.2mmol/L(IQR:1.0,1.5),respectively.The identified risk factors for malnutrition based on the PG-SGA score were age(0.05±0.01,p=0.002),BMI(-0.34±0.04,p<0.001),having a medical co-morbidity(0.95±0.33,p=0.004),receiving radiotherapy(1.52±0.31,p<0.001),the serum albumin level(-0.18±0.03,p<0.001),and the HDL-C(-1.12±0.35,p=0.001)as indicated by a linear regression analysis.Conclusions A higher PG-SGA score is positively associated with the age of the patient,having a medical co-morbidity,and receiving radiotherapy,and is negatively related to the patients’BMI and serum albumin and HDL-C levels.

Validity of the Chinese Version of the Patient-Generated Subjective Global Assessment (PG-SGA) in Lung Cancer Patients

The prevalence of malnutrition is high among oncology patients in China. Although the Patient- Generated Subjective Global Assessment (PG-SGA) is widely recognized as an important nutritional assessment tool, it has not been validated for Chinese cancer patients. The purpose of this study was to conduct an analysis of nutrition screening and assessment data to validate the Chinese version of the PG-SGA in Chinese patients with lung cancer. This was an observational, cross-sectional study of 2,000 consecutive adult patients with lung cancer treated at several tertiary hospitals in China. Anthropometric and patient descriptive data were collected. The PG-SGA generated a score for the nutritional risk and a global rating for the nutritional status. The internal consistency, external consistency, and construct validity were evaluated, and a known-groups comparison and principal component analyses were conducted to evaluate the reliability and validity of the PG-SGA. The known-groups comparison demonstrated the ability of the PG-SGA to differentiate lung cancer patients of different nutritional and body mass index (BMI) groups. A confirmatory factor analysis supported the original four-factor structure of the PG-SGA. In terms of the internal and external consistency, the PG-SGA demonstrated intra-class correlation coefficients (ICC) up to 0.987. Alternative form validity was also demonstrated between Box 4 of the PG-SGA and the Karnofsky Performance Status score, with excellent external consistency (r = 0.972, P < 0.001). The construct validity was supported, and selected questionnaire dimensions were evident in the principal component analysis. Significant Spearman correlations (P < 0.001) were demonstrated. The Chinese version of the PG-SGA demonstrated significant reliability and sufficient exploratory properties to support its validity. It seems to be a valid tool that can be used to access the nutritional status of Chinese lung cancer patients. The validity of the PG-SGA in Chinese cancer patients warrants further investigation in other cancer types.

Distinct Gene Expression Profile Distinguishes Increased Metabolic Activity in Spontaneously Hyperactive Rats While Sedentary from That Induced by Exercise

The Spontaneously-Running Tokushima Shikoku (SPORTS) strain is an original line derived from Wistar rats, which spontaneously runs >6 km/day on wheels, and has better glucose tolerance and less fat than Wistar rats. However, the molecular mechanism that contributes to the increased metabolic activity in SPORTS rats is unknown. The present study aimed to characterize the gene expression profiles of skeletal muscles in SPORTS rats housed under sedentary (SED) conditions. We found that the expression levels of genes encoding mitochondrial respiratory chain enzymes such as ATP synthase 6 (mt-Atp6) and cytochrome c oxidase subunit 6c (Cox6c), were higher in the soleus (SOL) muscles of SED SPORTS than in SED Wistar rats. The ratio of type IIa myofibers was higher and glucose tolerance was better in SED SPORTS than in Wistar rats that were sedentary and trained daily on treadmills, respectively. We then investigated candidate genes that might contribute to the better glucose tolerance of SED SPORTS rats using DNA microarray analysis. Among 116 upregulated genes in the SOL muscles of SED SPORTS rats, only 19 were also increased in trained Wistar rats. We focused on v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (Erbb3), which was associated with glucose transport in myocytes, and found higher expression levels in the SOL muscles of SED SPORTS than in SED Wistar rats. The SOL muscles of SED SPORTS rats also contained more activity of β-hydroxyacylCoA dehydrogenase, a key enzyme of β-oxidation, indicating enhanced lipid oxidation. These findings suggest that increased metabolic activity in skeletal muscle (especially the SOL muscle) of SPORTS rats is congenital and that gene expression profiles of SPORTS rats and Trained Wistar rats are different.

Validity of the Chinese Version of the Patient-Generated Subjective Global Assessment (PG-SGA) in Gastric Cancer Patients

Purpose Malnutrition is severe among gastric cancer patients in China. While the Patient-Generated Subjective Global Assessment (PG-SGA) is a widely used nutritional assessment tool, the validation for Chinese patients with gastric cancer has not been performed yet. The aim of this research is to validate the Chinese version of the PGSGA in Chinese gastric cancer patients by conducting analyses of nutrition screening and assessment data. Methods Two thousand consecutive adult patients with gastric cancer were included in this observational, cross-sectional study in several tertiary hospitals in China. A survey was made among those patients, which included several questionnaires and some anthropometric parameters. We calculated the parameters to validate the use of PG-SGA categorizing the nutritional status of gastric cancer patients. Then we performed statistical analysis to evaluate the internal consistency, external consistency, and construct validity. Results This study verified the ability of the PG-SGA to differentiate gastric cancer patients into different nutritional groups. The confirmatory factor analysis verified the original four-factor structure of the PG-SGA. The internal and external consistency was measured by a concordance analysis which showed an intraclass correlation coefficients (ICC) of 0.987. The correlations of the Box 4 score with the Karnofsky performance status score demonstrated alternative form validity with good external consistency (Pearson, r = 0.643, P < 0.001). All three anthropometric dimensions of the PG-SGA were supported by principal component analysis. Spearman correlations (P < 0.001) were significant in the majority of tests. Conclusion The Chinese version of the PG-SGA is a valid tool to access the patients’ nutritional status for Chinese gastric patients.

Sex differences in the scored Patient-Generated Subjective Global Assessment in 19,528 cancer patients

Background:The scored Patient-Generated Subjective Global Assessment(PG-SGA)has been widely used to assess the nutritional status of cancer patients.The purpose of this study is to compare the differences in PG-SGA scores and the 7 domain scores of the PG-SGA in male and female cancer patients.Methods:This study was conducted at 72 hospitals from July 2013 to December 2018,a part of the Investigation on Nutritional Status and its Clinical Outcomes of Common Cancers.The PG-SGA was recorded to evaluate the nutritional status of patients.A total of 19,528 patients with 13 common malignancies were included in this study.Student t test and the χ^(2) test were applied to analyze the sex diferences in the 7 domain scores.The Cancer Genome Atlas(TCGA)database was used to analyze the expression levels of symptom-related genes.Results:There were significant sex dfferences in the PG-SGA(P=0.032),notably in patients with gastric cancer(male vs female:9.09±4.86 vs 9.58±5.07,P=0.005)and esophageal cancer(9.64±4.90 vs 10.46±4.96,P=0.011)and the average total PG-SGA of female patients was slightly higher than that of male patients(7.64±4.98 vs 7.77±5.14).The differences were mainly related to the weight,eating,symptom,as well as activity and physical function scores in the stratified analysis.Possible causes of the sex differences were the rates of nausea,vomiting,dry mouth,and other symptoms,in both gastric and esophageal cancer patients.Analysis of the TCGA database suggested that most of the related genes were sex neutral,except for genes related to dysphagia in gastric cancer(VEGFC was higher in female patients,VEGFA and VEGFB higher in male patients).Conclusions:There are sex differences in the PG-SGA scores in patients with various tumor types(female patients generally had higher scores than male patients),with differences mainly in the weight,eating,symptom,as well as activity and physical function scores.The sex differences in PG-SGA scores might be due to the differences in the clinical manifestations of the disease,and further studies should be carried out to investigate other factors influencing the PG-SGA scores in cancer patients.This study provides basic data supporting the individualized nutritional treatment of cancer patients in clinical practice.