Combined effects of high sensitivity C-reactive protein and triglyceride-glucose index on risk of cardiovascular disease among middle-aged and older Chinese: Evidence from the China Health and Retirement Longitudinal Study.

BACKGROUND AND AIMS: High sensitivity C-reactive protein (hsCRP) and triglyceride glucose (TyG) index were proved to be independent risk factors of cardiovascular disease (CVD). However, individual hsCRP or TyG index might not provide sufficient predictive value on CVD risk. The current study aimed to evaluate the cumulative effect of hsCRP and TyG index on CVD risk prospectively. METHODS AND RESULTS: A total of 9626 participants were enrolled in the analysis. The TyG index was calculated as ln(triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The primary outcome was new-onset CVD events (cardiac events or stroke), and the secondary outcomes were new-onset cardiac events and stroke, separately. Participants were divided into 4 groups through the median of hsCRP and TyG index. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportion hazard models. From 2013 to 2018, 1730 participants experienced CVD (570 stroke and 1306 cardiac events). Linear associations were found between hsCRP, TyG index, hsCRP/TyG ratio and CVD (all p < 0.05). Compared to participants with low hsCRP/low TyG index, multivariable adjusted HRs (95% CIs) for those with high hsCRP/high TyG index were 1.17 (1.03-1.37) for CVD. No interaction of hsCRP and TyG index was found on CVD (p-interaction ≥0.05). Furthermore, adding hsCRP and TyG index simultaneously to conventional risk model improved risk reclassification for CVD, stroke and cardiac events (all p < 0.05). CONCLUSION: The present study suggested combination of hsCRP and TyG index might better improved the ability for risk stratification of CVD among middle-aged and older Chinese.

Pain Incidence and Associated Risk Factors among Cancer Patients within 72 Hours after Surgery: A Large Retrospective Analysis.

BACKGROUND: A fundamental principle of pain management is to determine the distribution and causes of pain. However, relevant data among postoperative cancer patients based on a large amount of data remain sparse. OBJECTIVE: We aimed to investigate the incidence of postoperative pain in cancer patients and to explore the associated risk factors. METHODS: We retrospectively collected information on postoperative pain-evaluation records of cancer patients who underwent surgery between 1 January 2014 and 31 December 2019. Descriptive statistics were presented, and multinominal logistic regression analysis was performed to explore the risk factors associated with postoperative pain. RESULTS: Among the 11,383 patients included in the study, the incidence of mild/moderate to severe pain at the 24th hour after surgery was 74.9% and 18.3%, respectively. At the 48th and 72nd hour after surgery, the incidence of mild pain increased slightly, while the incidence of moderate to severe pain continued to decrease. Female patients experienced a higher risk of pain (ORs: 1.37-1.58). Undergoing endoscopic surgery was associated with a higher risk of pain (ORs: 1.40-1.56). Patients with surgical sites located in the respiratory system had a higher risk of pain compared to in the digestive system (ORs: 1.35-2.13), and other patients had a relatively lower risk of pain (ORs: 0.11-0.61). CONCLUSION: The majority of cancer patients experienced varying degrees of postoperative pain but may not receive adequate attention and timely treatment. Female, young age and endoscopic surgery were associated with increased pain risk, and effective identification of these high-risk groups had positive implications for enhanced postoperative pain management.

Synergism between the metabolic syndrome components and cancer incidence: results from a prospective nested case-control study based on the China Health and Retirement Longitudinal Study (CHARLS).

OBJECTIVES: Synergism between the metabolic syndrome (MetSyn) components and cancer incidence still remains inconclusive. We aimed to investigate the unique or joint role of MetSyn components in cancer onset. DESIGN: We conducted a prospective nested case-control study based on the China Health and Retirement Longitudinal Study. SETTING: An ongoing national representative longitudinal study included follow-up survey of people aged 45 years and older and their partners living in private households in China. PARTICIPANTS: There were 17 708 individuals included at baseline. A total of 306 incident cancers was identified during the follow-up. For every case, we used incidence-density sampling to match three concurrent cancer-free controls by age, sex, and both duration and calendar time of follow-up. Exposure of interest was any MetSyn diagnosis at baseline. RESULTS: We observed elevation in cancer risk associated with MetSyn in a significant way when the number of MetSyn components was over three (OR: 1.88; 95% CI: 1.19 to 2.97), or when components contained any of elevated triglycerides (OR: 1.61; 95% CI: 1.05 to 2.48), reduced high-density lipoprotein (HDL) cholesterol (OR: 2.33; 95% CI: 1.40 to 3.86) or elevated blood pressure (OR: 1.65; 95% CI: 1.04 to 2.59) after consistent multiple adjustments in different models. The highest cancer risk was in the female reproductive system and breast cancer (OR: 4.22; 95% CI: 1.62 to 10.95) followed by digestive system (OR: 1.67; 95% CI: 1.11 to 2.53). Sensitivity analyses showed similar results after first follow-up was excluded. However, any unique MetSyn component was not associated with increased cancer risk. Interestingly, the reduced HDL was observed to be widely associated with over twofold increased risk of cancer, only when together with other MetSyn components. CONCLUSION: MetSyn components, in a collaborative manner rather than its unique component, were associated with elevated cancer risk. Not only obesity but even subtle metabolic disturbances may give rise to cancer.

Comparing Long-Term Survival Outcomes for Muscle-Invasive Bladder Cancer Patients Who Underwent with Radical Cystectomy and Bladder-Sparing Trimodality Therapy: A Multicentre Cohort Analysis.

Background: Although radical cystectomy (RC) is the clinical practice guideline-recommended treatment of muscle-invasive bladder cancer (MIBC), bladder-sparing trimodality therapy (TMT) has emerged as a valid treatment option. Findings comparing the survival outcomes for MIBC patients who underwent RC and TMT are inconclusive. Objective: We designed a large hospital-based multicohort study to compare the effectiveness of TMT with RC. Methods: Information on deaths was jointly retrieved from EMR (electronic medical record), cause of death registry, and chronic disease surveillance as well as study-specific questionnaire. To avoid the systematical difference between patients who received two modalities, RC-MIBC cohort was propensity score-matched to TMT-MIBC cohort, and the Cox proportional hazard regression was used to calculate the overall survival (OS) and disease-specific survival (DSS). Results: There were 891 MIBC patients treated with RC and another 891 MIBC patients who underwent with TMT in the propensity score matching. Comparable effectiveness between two modalities was observed for DSS (HR, 1.20; 95% confidence interval (CI), 0.94 to 1.49) and OS (HR, 1.17; 95% CI, 0.91 to 1.43) according to multiple adjustment after a median follow-up of approximately 9.3 years. However, a relatively higher mortality rate around 5 years after TMT treatment was found compared to RC (HR, 1.26; 95% CI, 1.01 to 1.53). The respective 5-year OS rates were 69% and 73% for TMT cohort and RC cohort, respectively. Conclusions: Our findings supported that MIBC patients with TMT yielded survival outcomes comparable to MIBC patients who underwent RC overall. Treatment options should be suggested considering patients' age and willingness.

Hormone replacement therapy in relation to the risk of colorectal cancer in women by BMI: a multicentre study with propensity score matching.

BACKGROUND: Epidemiological evidence about hormone replacement therapy and colorectal carcinogenesis by demographic and clinical traits remains unclear. We aimed to assess this postulated association in a large multicentre study and further explore the modification effect by BMI and others. METHODS: We retrospectively collected records of women diagnosed with colorectal cancer (CRC) at the age of 50 years and older during 2014-2017 and their HRT dispensing prior to CRC diagnosis in three tertiary hospitals in China. CRC cases were matched with controls at a ratio of 1:3 using nearest neighbour propensity scores matching to better control for the remaining imbalance between groups, which generated a total of 824 cases with 2472 controls. RESULTS: Our study confirmed the inversed association between colorectal cancer risk and hormone replacement therapy (OR, 0.62; 95% CI, 0.54-0.75), which was more prominent among women having multiple HRT dispenses (OR, 0.60; 95% CI, 0.52-0.76). Furthermore, significant associations were consistently observed for the short-term (OR, 0.69; 95% CI, 0.57-0.88), middle-term (OR, 0.51; 95% CI, 0.41-0.66), and long-term HRT users (OR, 0.70; 95% CI, 0.43-0.90). Estrogen-related regimen reduced CRC risk more than progestogen-only. We, for the first time, found that the modifying effect of BMI on HRT use and CRC risk was in different ways when BMI was categorized by a medium level of 27. CONCLUSION: Our findings mainly suggest that there might be a different mechanism for the reversed association between HRT and colorectal tumorigenesis by BMI level, providing thoughts on clinical treatment of CRC.

Risk of Death in Colorectal Cancer Patients with Multi-morbidities of Metabolic Syndrome: A Retrospective Multicohort Analysis.

PURPOSE: The prevalence of multi-morbidities with colorectal cancer (CRC) is known to be increasing. Particularly prognosis of CRC patients co-diagnosed with metabolic syndrome (MetSyn) was largely unknown. We aimed to examine the death risk of CRC patients according to the multiple MetSyn morbidities. MATERIALS AND METHODS: We identified CRC patients with MetSyn from the electronic medical records (EMR) systems in five independent hospitals during 2006-2011. Information on deaths was jointly retrieved from EMR, cause of death registry and chronic disease surveillance as well as study-specific questionnaire. Cox proportional hazards regression was used to calculate the overall and CRC-specific hazards ratios (HR) comparing MetSyn CRC cohort with reference CRC cohort. RESULTS: A total of 682 CRC patients in MetSyn CRC cohort were identified from 24 months before CRC diagnosis to 1 month after. During a median follow-up of 92 months, we totally observed 584 deaths from CRC, 245 being in MetSyn cohort and 339 in reference cohort. Overall, MetSyn CRC cohort had an elevated risk of CRC-specific mortality (HR, 1.49; 95% confidence interval [CI], 1.07 to 1.90) and overall mortality (HR, 1.43; 95% CI, 1.09 to 1.84) compared to reference cohort after multiple adjustment. Stratified analyses showed higher mortality risk among women (HR, 1.87; 95% CI, 1.04 to 2.27) and specific components of MetSyn. Notably, the number of MetSyn components was observed to be significantly related to CRC prognosis. CONCLUSION: Our findings supported that multi-morbidities of MetSyn associated with elevated death risk after CRC. MetSyn should be considered as an integrated medical condition more than its components in CRC prognostic management.

A novel prognostic biomarker for muscle invasive bladder urothelial carcinoma based on 11 DNA methylation signature.

Muscle-invasive bladder urothelial carcinoma (MIBC) is a highly invasive cancer, which leads to prevalent recurrence and poor prognosis. Exploring the association of DNA methylation and the prognosis of MIBC will thus be of important value in clinical management and treatment. Bumphunter method and adaptive lasso regression were used to explore the relationship between different methylation regions (DMRs) and the prognosis of MIBC. Next, we constructed a risk prognosis model and validated this model. Moreover, the performance of this risk model was examined by using time-dependent receiver operating characteristic curve (ROC). We identified 58,449 different methylation sites and 490 different methylation regions. Among them, 11 DMRs were associated with the prognosis of MIBC through rigorous screening. Through the linear combination of 11 DMRs, a putative marker was developed, which can distinguish the survival risk in both the training dataset (HR = 2.58, 95% CI = (1.64, 4.05)) and the verification dataset (HR = 2.77, 95% CI = (1.25, 6.15)). Relatively high predictive values were observed from this model for training dataset (AUC = 0.791) and verification dataset (AUC = 0.668). Stratified analysis showed that the association was independent of gender. A nomogram was additionally generated to predict 5-year survival probability containing risk score and pathological stage. Its performance was evaluated by applying calibration curve. The methylation signature risk model based on 11 DMRs may be a reliable prognostic signature for MIBC, which provides new insights into development of individualized therapy for MIBC.

A Novel Biomarker Based on miRNA to Predict the Prognosis of Muscle-Invasive Bladder Urothelial Carcinoma.

Muscle-invasive bladder urothelial carcinoma (MIBC) is characteristic of high mortality and high recurrence. Distinguishing the prognostic risk of MIBC at the molecular level of miRNA expression is rarely performed and thus of great significance for the management and treatment of MIBC in clinics. Adaptive lasso Cox's proportional hazards model was used to explore the relationship between differential expression miRNAs (DEmiRNAs) and MIBC survival. Furthermore, we evaluated the epithelial-mesenchymal transition (EMT) score and immune infiltration abundance by exploring EMT signature genes and TIMER database, respectively. A total of 8 DEmiRNAs were detected to be associated with the survival rate of MIBC by using the lasso Cox algorithm. Through the linear combination of these 8 DEmiRNAs, we constructed a calculated marker, which could be used to distinguish the prognosis risk in both TCGA dataset (HR = 2.03, 95% CI = (1.47, 2.83)) and independent validation dataset (HR = 7.74, 95% CI = (1.05, 56.93)). Meanwhile, the constructed marker had reasonably high predictive values of the AUC (area under the curve) in the TCGA dataset and validation dataset being 0.73 and 0.63, respectively. In addition, we observed that the expression values of let-7c, miR-100, and miR-145 were associated with EMT score and the abundance of macrophage in tumor tissue as well. This newly identified risk score signature based on the combination of 8 miRNAs could significantly predict the prognostic risk of MIBC and might provide insight into immunotherapy and targeted therapy of MIBC.