Efficacy Analysis of Multidisciplinary Treatment for Wilm’s Tumor in Single Center

Objective: To analyze the efficacy of multidisciplinary treatment (MDT) for Wilm’s tumor (WT) in Kunming Children’s Hospital, and investigate the risk factors affecting the prognosis of WT.Method: The clinic-pathological data were collected and analyzed in patients with unilateral WT treated in Kunming Children's Hospital from January 2017 to July 2021. Research objects were selected according to inclusion criteria and exclusion criteria. The risk factors and independent risk factors that affect the prognosis of patients with WT were determined by Kaplan-Meier survival analysis and Cox proportional hazards model, respectively. Outcome: A total of 68 children were included in this study, and the 5-year overall survival (OS) rate was 92.65%. Kaplan-Meier survival analysis results showed that ethnicity (P=0.020), the tumor volume of resection (P=0.001), histological type (P<0.001), and postoperative recurrence (P<0.001) were the factors affecting the prognosis of children with WT. The results of the Cox proportional hazards model showed that only the histological type (P=0.028) was the independent risk factor for the prognosis of WT.Conclusion: The efficacy of MDT for WT was satisfying. The histological type has important predictive value for the prognosis of WT, and the patient with unfavorable histology has a poor prognosis.

The Association Between Long-Term Exposure to Particulate Matter and Incidence of Hypertension Among Chinese Elderly: A Retrospective Cohort Study

Background and Objectives: Studies that investigate the links between particulate matter ≤2. 5 μm (PM2.5) and hypertension among the elderly population, especially those including aged over 80 years, are limited. Therefore, we aimed to examine the association between PM2.5 exposure and the risk of hypertension incidence among Chinese elderly.Methods: This prospective cohort study used 2008, 2011, 2014, and 2018 wave data from a public database, the Chinese Longitudinal Healthy Longevity Survey, a national survey investigating the health of those aged over 65 years in China. We enrolled cohort participants who were free of hypertension at baseline (2008) from 706 counties (districts) and followed up in the 2011, 2014, and 2018 survey waves. The annual PM2.5 concentration of 706 counties (districts) units was derived from the Atmospheric Composition Analysis Group database as the exposure variable, and exposure to PM2.5 was defined as 1-year average of PM2.5 concentration before hypertension event occurrence or last interview (only for censoring). A Cox proportional hazards model with penalized spline was used to examine the non-linear association between PM2.5 concentration and hypertension risk. A random-effects Cox proportional hazards model was built to explore the relationship between each 1 μg/m3, 10 μg/m3 and quartile increment in PM2.5 concentration and hypertension incidence after adjusting for confounding variables. The modification effects of the different characteristics of the respondents were also explored.Results: A total of 7,432 participants aged 65–116 years were enrolled at baseline. The median of PM2.5 exposure concentration of all the participants was 52.7 (inter-quartile range, IQR = 29.1) μg/m3. Overall, the non-linear association between PM2.5 and hypertension incidence risk indicated that there was no safe threshold for PM2.5 exposure. The higher PM2.5 exposure, the greater risk for hypertension incidence. Each 1 μg/m3 [adjusted hazard ratio (AHR): 1.01; 95% CI: 1.01–1.02] and 10 μg/m3 (AHR: 1.12; 95% CI: 1.09–1.16) increments in PM2.5, were associated with the incidence of hypertension after adjusting for potential confounding variables. Compared to first quartile (Q1) exposure, the adjusted HRs of hypertension incidence for the Q2, Q3 and Q4 exposure of PM2.5 were 1.31 (95% CI: 1.13–1.51), 1.35 (95% CI: 1.15–1.60), and 1.83 (95% CI: 1.53–2.17), respectively. The effects appear to be stronger among those without a pension, living in a rural setting, and located in central/western regions.Conclusion: We found no safe threshold for PM2.5 exposure related to hypertension risk, and more rigorous approaches for PM2.5 control were needed. The elderly without a pension, living in rural and setting in the central/western regions may be more vulnerable to the effects of PM2.5 exposure.

A novel 14-gene signature for overall survival in lung adenocarcinoma based on the Bayesian hierarchical Cox proportional hazards model

There have been few investigations of cancer prognosis models based on Bayesian hierarchical models. In this study, we used a novel Bayesian method to screen mRNAs and estimate the effects of mRNAs on the prognosis of patients with lung adenocarcinoma. Based on the identified mRNAs, we can build a prognostic model combining mRNAs and clinical features, allowing us to explore new molecules with the potential to predict the prognosis of lung adenocarcinoma. The mRNA data (n = 594) and clinical data (n = 470) for lung adenocarcinoma were obtained from the TCGA database. Gene set enrichment analysis (GSEA), univariate Cox proportional hazards regression, and the Bayesian hierarchical Cox proportional hazards model were used to explore the mRNAs related to the prognosis of lung adenocarcinoma. Multivariate Cox proportional hazard regression was used to identify independent markers. The prediction performance of the prognostic model was evaluated not only by the internal cross-validation but also by the external validation based on the GEO dataset (n = 437). With the Bayesian hierarchical Cox proportional hazards model, a 14-gene signature that included CPS1, CTPS2, DARS2, IGFBP3, MCM5, MCM7, NME4, NT5E, PLK1, POLR3G, PTTG1, SERPINB5, TXNRD1, and TYMS was established to predict overall survival in lung adenocarcinoma. Multivariate analysis demonstrated that the 14-gene signature (HR 3.960, 95% CI 2.710–5.786), T classification (T1, reference; T3, HR 1.925, 95% CI 1.104–3.355) and N classification (N0, reference; N1, HR 2.212, 95% CI 1.520–3.220; N2, HR 2.260, 95% CI 1.499–3.409) were independent predictors. The C-index of the model was 0.733 and 0.735, respectively, after performing cross-validation and external validation, a nomogram was provided for better prediction in clinical application. Bayesian hierarchical Cox proportional hazards models can be used to integrate high-dimensional omics information into a prediction model for lung adenocarcinoma to improve the prognostic prediction and discover potential targets. This approach may be a powerful predictive tool for clinicians treating malignant tumours.

Diagnostic and prognostic value of presepsin and procalcitonin in non-infectious organ failure, sepsis, and septic shock: a prospective observational study according to the Sepsis-3 definitions

Background We investigated the diagnostic and prognostic value of presepsin among patients with organ failure, including sepsis, in accordance with the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Methods This prospective observational study included 420 patients divided into three groups: non-infectious organ failure (n = 142), sepsis (n = 141), and septic shock (n = 137). Optimal cut-off values of presepsin to discriminate between the three groups were evaluated using receiver operating characteristic curve analysis. We determined the optimal cut-off value of presepsin levels to predict mortality associated with sepsis and performed Kaplan–Meier survival curve analysis according to the cut-off value. Cox proportional hazards model was performed to determine the risk factors for 30-day mortality. Results Presepsin levels were significantly higher in sepsis than in non-infectious organ failure cases (p < 0.001) and significantly higher in patients with septic shock than in those with sepsis (p = 0.002). The optimal cut-off value of the presepsin level to discriminate between sepsis and non-infectious organ failure was 582 pg/mL (p < 0.001) and between sepsis and septic shock was 1285 pg/mL (p < 0.001). The optimal cut-off value of the presepsin level for predicting the 30-day mortality was 821 pg/mL (p = 0.005) for patients with sepsis. Patients with higher presepsin levels (≥ 821 pg/mL) had significantly higher mortality rates than those with lower presepsin levels (< 821 pg/mL) (log-rank test; p = 0.004). In the multivariate Cox proportional hazards model, presepsin could predict the 30-day mortality in sepsis cases (hazard ratio, 1.003; 95% confidence interval 1.001–1.005; p = 0.042). Conclusions Presepsin levels could effectively differentiate sepsis from non-infectious organ failure and could help clinicians identify patients with sepsis with poor prognosis. Presepsin was an independent risk factor for 30-day mortality among patients with sepsis and septic shock.

Factors Related to the Delayed Cure of Hemifacial Spasm after Microvascular Decompression: An Analysis of 175 Consecutive Patients

Detailed studies assessing the factors related to delayed cure of hemifacial spasm (HFS) after microvascular decompression (MVD) are sparse. We aimed to evaluate the effect of 11 clinical factors on the time until the patient became spasm free after MVD. We enrolled 175 consecutive patients with HFS who underwent MVD between 2012 and 2018. The end point was defined as the time point at which the patient became spasm free based on the outpatient interview. Patients were divided into six groups depending on when they became spasm free after the operation, as follows: <7 days (n = 62), 7 days to 1 month (n = 28), 1 to 3 months (n = 38), 3 to 6 months (n = 25), 6 to 12 months (n = 17), and >12 months (n = 5). The median time to become spasm free after MVD was 30.0 days. Association of 11 factors (age, sex, laterality, number of offending arteries, vertebral artery compression, number of compression sites, compression at root detachment zone, preoperative Botox treatment, indentation of the brain stem on preoperative magnetic resonance image, transposition, and interposition) with spasm-free rate was assessed using the Cox's proportional hazards model. Spasm-free rate curve after MVD for the significant factor was obtained using the Kaplan–Meier method. In univariate and multivariate analyses, nontransposition was significantly related to delayed HFS cure after MVD (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.42, 0.87; p = 0.0068 and HR, 0.60; CI, 0.43, 0.85; p = 0.042, respectively). The spasm-free rate was higher in the transposition than in the nontransposition group (p = 0.0013). As shortening the time until spasm free after MVD improves patients' quality of life, transposition should be recommended. Prediction of spasm-free time could relieve the anxiety of postoperative patients.

High-Dimensional Mediation Analysis Based on Additive Hazards Model for Survival Data

Mediation analysis has been extensively used to identify potential pathways between exposure and outcome. However, the analytical methods of high-dimensional mediation analysis for survival data are still yet to be promoted, especially for non-Cox model approaches. We propose a procedure including “two-step” variable selection and indirect effect estimation for the additive hazards model with high-dimensional mediators. We first apply sure independence screening and smoothly clipped absolute deviation regularization to select mediators. Then we use the Sobel test and the BH method for indirect effect hypothesis testing. Simulation results demonstrate its good performance with a higher true-positive rate and accuracy, as well as a lower false-positive rate. We apply the proposed procedure to analyze DNA methylation markers mediating smoking and survival time of lung cancer patients in a TCGA (The Cancer Genome Atlas) cohort study. The real data application identifies four mediate CpGs, three of which are newly found.