Elevation of serum human epididymis protein 4 (HE4) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as predicting factors for the occurrence of acute kidney injury on chronic kidney disease: a single-center retrospective self-control study.

Objectives: To evaluate whether novel biomarkers of renal injury, serum HE4 and NT-proBNP could predict acute kidney injury (AKI) on chronic kidney disease (CKD) (A on C) and assess the specificity and efficiency of serum creatinine (SCr), HE4 and NT-proBNP in identifying potential AKI. Meanwhile, the potential early-warning value of HE4 and NT-proBNP in CKD patients was explored. Methods: We performed a single-center, retrospective cohort study of 187 adult CKD patients. 32 AKI (grades 1-2) patients with pre-existing CKD (stages 3-5) were Group 1, 59 patients of CKD (stages 4-5) were Group 2. Another 96 patients of CKD (stages 1-3) were Group 3. All patients received general treatments, Group 1 patients received Chinese herb formulation (Chuan Huang Fang-Ⅱ, CHF-Ⅱ) simultaneously. These 155 CKD (stages 1-5) without AKI patients were observed for descriptive analysis. Results: HE4 in Group 1 (860.63 ± 385.40) was higher than that in Group 2 (673.86 ± 283.58) before treatments. BUN, SCr, UA, NGAL, IL18, HE4 and NT-proBNP in Group 1 were lower, while eGFR was higher (p < 0.01, after vs. before treatments). In Group 1, both HE4 and NT-proBNP were positively correlated with SCr (respectively r = 0.549, 0.464) before treatments. The diagnostic performance of serum HE4 and NT-proBNP for A on C was 351.5 pmol/L, 274.5 pg/mL as the optimal cutoff value Area Under Curve (AUC) 0.860 (95% CI: 0.808 - 0.913, p < 0.001), [AUC 0.775 (95% CI: 0.697 - 0.853, p < 0.001), with a sensitivity and specificity of 100% and 66.5%, 87.5% and 48.8%, respectively]. In Group 2, serum HE4 was correlated with SCr (r = 0.682, p < 0.01) before treatments. Serum HE4 and NT-proBNP were elevated in advanced CKD stages, and were increased as CKD stages progressed with statistical significance. Conclusion: This work indicated serum HE4 and NT-proBNP should elevate in A on C and CKD patients, HE4 is positively correlated with the disease severity, and patients with higher HE4 and NT-proBNP usually have poorer prognosis. Thus, serum HE4 and NT-proBNP are impactful predictors of A on C. Additionally, serum HE4 and NT-proBNP have the potential to evaluate clinical efficacy of A on C.

Development and validation of postoperative circulating tumor DNA combined with clinicopathological risk factors for recurrence prediction in patients with stage I-III colorectal cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) detection following curative-intent surgery could directly reflect the presence of minimal residual disease, the ultimate cause of clinical recurrence. However, ctDNA is not postoperatively detected in ≥ 50% of patients with stage I-III colorectal cancer (CRC) who ultimately recur. Herein we sought to improve recurrence risk prediction by combining ctDNA with clinicopathological risk factors in stage I-III CRC. METHODS: Two independent cohorts, both consisting of early-stage CRC patients who underwent curative surgery, were included: (i) the discovery cohort (N = 124) with tumor tissues and postoperative plasmas for ctDNA determination; and (ii) the external validation cohort (N = 125) with available ctDNA results. In the discovery cohort, somatic variations in tumor tissues and plasmas were determined via a 733-gene and 127-gene next-generation sequencing panel, respectively. RESULTS: In the discovery cohort, 17 of 108 (15.7%) patients had detectable ctDNA. ctDNA-positive patients had a significantly high recurrence rate (76.5% vs. 16.5%, P < 0.001) and short recurrence-free survival (RFS; P < 0.001) versus ctDNA-negative patients. In addition to ctDNA status, the univariate Cox model identified pathologic stage, lymphovascular invasion, nerve invasion, and preoperative carcinoembryonic antigen level associated with RFS. We combined the ctDNA and clinicopathological risk factors (CTCP) to construct a model for recurrence prediction. A significantly higher recurrence rate (64.7% vs. 8.1%, P < 0.001) and worse RFS (P < 0.001) were seen in the high-risk patients classified by the CTCP model versus those in the low-risk patients. Receiver operating characteristic analysis demonstrated that the CTCP model outperformed ctDNA alone at recurrence prediction, which increased the sensitivity of 2 year RFS from 49.6% by ctDNA alone to 87.5%. Harrell's concordance index, calibration curve, and decision curve analysis also suggested that the CTCP model had good discrimination, consistency, and clinical utility. These results were reproduced in the validation cohort. CONCLUSION: Combining postoperative ctDNA and clinical risk may better predict recurrence than ctDNA alone for developing a personalized postoperative management strategy for CRC.

Multi-institutional development and external validation of machine learning-based models to predict relapse risk of pancreatic ductal adenocarcinoma after radical resection.

BACKGROUND: Surgical resection is the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC) and the survival of patients after radical resection is closely related to relapse. We aimed to develop models to predict the risk of relapse using machine learning methods based on multiple clinical parameters. METHODS: Data were collected and analysed of 262 PDAC patients who underwent radical resection at 3 institutions between 2013 and 2017, with 183 from one institution as a training set, 79 from the other 2 institution as a validation set. We developed and compared several predictive models to predict 1- and 2-year relapse risk using machine learning approaches. RESULTS: Machine learning techniques were superior to conventional regression-based analyses in predicting risk of relapse of PDAC after radical resection. Among them, the random forest (RF) outperformed other methods in the training set. The highest accuracy and area under the receiver operating characteristic curve (AUROC) for predicting 1-year relapse risk with RF were 78.4% and 0.834, respectively, and for 2-year relapse risk were 95.1% and 0.998. However, the support vector machine (SVM) model showed better performance than the others for predicting 1-year relapse risk in the validation set. And the k neighbor algorithm (KNN) model achieved the highest accuracy and AUROC for predicting 2-year relapse risk. CONCLUSIONS: By machine learning, this study has developed and validated comprehensive models integrating clinicopathological characteristics to predict the relapse risk of PDAC after radical resection which will guide the development of personalized surveillance programs after surgery.

The Effect of Indoor Daylight Levels on Hospital Costs and Length of Stay of Patients Admitted to General Surgery.

BACKGROUND: Indoor daylight levels can directly affect the physical and psychological state of people. However, the effect of indoor daylight levels on the clinical recovery process of the patient remains controversial. This study was to evaluate the effect of indoor daylight levels on hospital costs and the average length of stay (LOS) of a large patient population in general surgery wards. METHODS: Data were collected retrospectively and analyzed of patients in the Second Affiliated Hospital of Zhejiang University, School of Medicine between January 2015 and August 2020. We measured daylight levels in the patient rooms of general surgery and assessed their association with the total hospital costs and LOS of the patients. RESULTS: A total of 2,998 patients were included in this study with 1,478 each assigned to two daylight level groups after matching. Overall comparison of hospital total costs and LOS among patients according to daylight levels did not show a significant difference. Subgroup analysis showed when exposed to higher intensity of indoor daylight, illiterate patients had lower total hospital costs (CNY ¥13070.0 vs. ¥15210.3, p = 0.018) and shorter LOS (7 vs. 10 days, p = 0.011) as compared to those exposed to a lower intensity. CONCLUSIONS: Indoor daylight levels were not associated with the hospital costs and LOS of patients in the wards of general surgery, except for those who were illiterate. It might be essential to design guidelines for medical staff and healthcare facilities to enhance the indoor environmental benefits of daylight for some specific populations.

Susceptibility loci for metabolic syndrome and metabolic components identified in Han Chinese: a multi-stage genome-wide association study.

Metabolic syndrome (MetS), a cluster of metabolic disturbances that increase the risk for cardiovascular disease and diabetes, was because of genetic susceptibility and environmental risk factors. To identify the genetic variants associated with MetS and metabolic components, we conducted a genome-wide association study followed by replications in totally 12,720 participants from the north, north-eastern and eastern China. In combined analyses, independent of the top known signal at rs651821 on APOA5, we newly identified a secondary triglyceride-associated signal at rs180326 on BUD13 (Pcombined = 2.4 × 10-8 ). Notably, by an integrated analysis of the genotypes and the serum levels of APOA5, BUD13 and triglyceride, we observed that BUD13 was another potential mediator, besides APOA5, of the association between rs651821 and serum triglyceride. rs671 (ALDH2), an east Asian-specific common variant, was found to be associated with MetS (Pcombined = 9.7 × 10-22 ) in Han Chinese. The effects of rs671 on metabolic components were more prominent in drinkers than in non-drinkers. The replicated loci provided information on the genetic basis and mechanisms of MetS and metabolic components in Han Chinese.

Higher Levels of Magnesium and Lower Levels of Calcium in Whole Blood Are Positively Correlated with the Metabolic Syndrome in a Chinese Population: A Case-Control Study.

Magnesium (Mg) and calcium (Ca) are essential for numerous kinds of metabolisms in human body. To investigate the associations between Mg and Ca and the ratio of Ca to Mg (Ca/Mg) in whole blood with metabolic syndrome (MetS) in a Chinese population, a matched case-control study including 204 MetS patients and 204 healthy controls (aged 48-89) was carried out in 2011. MetS were diagnosed according to the criteria of Chinese Diabetes Society. Controls had no abnormal metabolic components and were matched with cases by age, gender and region. Blood samples were collected in the morning after an overnight fast. Whole blood Mg and Ca were determined by flame atomic absorption spectrometry. Subjects who were male constituted 44.1% of the part of this study. The average age was 64.0 ± 7.18, and the average body mass index was 24.3 ± 3.75. The MetS group showed significantly higher Mg and lower Ca and Ca/Mg as compared with the control group. Comparing with the bottom tertile (T1) of Mg, increased ORs for MetS were found in median tertile (T2) and top tertile (T3) of Mg. For Ca, T2 and T3 were negatively associated with MetS. Inverse relationship was also found between Ca/Mg ratio and MetS. Our findings suggested that increased Mg and decreased Ca and Ca/Mg in whole blood were correlated with MetS in Chinese adults.

High levels of plasma selenium are associated with metabolic syndrome and elevated fasting plasma glucose in a Chinese population: A case-control study.

BACKGROUND: Selenium is important for human health and involved in various metabolic processes. Deficiency of selenium associates with increased risk for cancer and cardiovascular diseases. There has been an increase use of selenium supplements for the treatment of autoimmune thyroid conditions. However, the potential biological effects of selenium overload arouse the public concern. The aim of this study was to investigate the associations of plasma selenium concentrations of adults with metabolic syndrome (MS) in Chinese population. METHODS: A matched case-control study including 204 metabolic syndrome patients and 204 healthy controls was conducted in 2012. The MS cases were defined according to the criteria of Chinese Diabetes Society (CDS). Healthy controls without abnormality of metabolic components were matched with cases in age, gender and region. Plasma concentrations of selenium were determined by graphite furnace atomic absorption spectrometry (GFAAS). Fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL), and low density lipoprotein cholesterol (LDL) were detected by automatic biochemical analyzer. RESULTS: The median levels of plasma selenium in MS group were 146.3 (107.3-199.4)µg/L, which were significantly higher than that in the control group (127.4: 95.7-176.0)µg/L; Plasma levels of selenium were related to the risk of MS in dose-response manner. Risk of MS was significantly higher in subjects with plasma selenium in the highest tertile (T3: ≥176.0µg/L) compared to those in the lowest tertile (T1: <95.7µg/L) [odds ratio (OR)=2.416 (95% CI: 1.289-4.526)]. The plasma levels of selenium were positively correlated with fasting plasma glucose (FPG) (rs=0.268, P<0.001). Plasma selenium at the median (T2: 95.7-176.0µg/L) or upper tertile (T3: ≥176.0µg/L) was associated with increased risk of elevated FPG (defined by FPG≥6.1mmol/L) as compared with the lowest tertile (T1: ≤95.7µg/L) [T2 vs. T1, OR=3.487 (1.738-6.996); T3 vs. T1, OR=6.245 (3.005-12.981)]. CONCLUSIONS: Higher levels of plasma selenium might increase the risk of metabolic syndrome and elevated fasting plasma glucose. Selenium supplements should be used with prudence for CVD and cancer prevention.

Waist-to-Height Ratio: a simple, effective and practical screening tool for childhood obesity and metabolic syndrome.

OBJECTIVE: This study aimed to evaluate the diagnostic value of Waist-to-Height Ratio in early detection of obesity and metabolic syndrome in Chinese children and adolescents. METHOD: A cross-sectional study was conducted in six cities in China in 2010 with 16,914 children and adolescents aged 7-17 years. Participants were randomly divided into the training and testing sets. Diagnostic values were estimated using sensitivity, specificity and areas under receiver operating characteristic curves. RESULTS: The coefficients of variation of Waist-to-Height Ratio among age groups were lower than that of body mass index and waist circumstance. The area under receiver operating characteristic curve of Waist-to-Height Ratio was 0.968 in boys and 0.949 in girls for general obesity evaluation, and 0.983 in boys and 0.984 in girls for central obesity. The optimal cut-offs of Waist-to-Height Ratio were 0.47 in boys and 0.45 in girls in the training set and validated in the testing set. For metabolic syndrome evaluation, the sensitivity and specificity were 0.858 and 0.825 in boys, 0.864 and 0.812 in girls under the suggested cut-offs. CONCLUSION: Waist-to-Height Ratio was a simple, effective and practical tool for mass screening childhood obesity and metabolic syndrome in China. It will have potential values in public health practice.